Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys Our ref.: Date I 2815 WO 22 August 2023 Applicant: IMOPHORON LIMITED Science Creates Old Market Midland Road Bristol, BS20JZ/GB Adenovirus penton-based virus-like particles The present invention relates to an adenovirus penton-based polypeptide assembly comprising (i) at least one pentamer of adenovirus penton base protomer polypeptides each having an adenovirus fiber protein binding cleft and (ii) at least one polypeptide (1) at least one adenovirus fiber protein N-terminal fragment specifically binding to the adenovirus fiber protein binding cleft of said penton base protomers, (2) a multimerization domain and (3a) a non-adenoviral peptide component and/or (3b) a drug or label covalently or non-covalently coupled to the multimerization domain or the non-adenoviral peptide. The invention further relates to methods for producing the adenovirus penton-based polypeptide assembly, pharmaceutical composition containing them, and to medical uses of the polypeptide assembly. The COVID19 pandemic continues to wreak havoc on communities and economies worldwide. In an unprecedented effort, vaccines as well as monoclonal antibody treatments to contain COVID-19 were developed and deployed, reducing hospitalizations and deaths, primarily in developed countries. In an unprecedented effort, a large number of COVID-19 vaccine candidates were developed at record speed , and several were authorized for emergency use or received full approval by regulatory agencies around the world. Among these, prominent examples include the mRNA vaccines available from Pfizer Inc. (New York, NY, USA) and Moderna Inc. (Cambridge, MA, USA), which use messenger RNA to instruct cells to produce the SARS_CoV-2 spike glycoprotein (S), a major vaccine target, to trigger an immune response. Other vaccines such as those available from AstraZeneca PLC (Cambridge, UK) and Johnson & Johnson Corp. (New Brunswick, NJ, USA) use adenovirus as a vector to induce production of SARS-CoV-2 S in the body. The vaccine from Novavax Inc. (Gaithersburg, MD, USA) uses recombinant S proteins attached to a lipidic matrix for immunization. These vaccines of the prior art vaccines have been shown to be effective in preventing COVID-19, with the mRNA vaccines exhibiting highest efficacy rates (~95%) albeit relatively short-lived (Hatcher et al. (2022) Vaccines (Basel) 10, https://doi.org:10.3390/vaccines10030393). All currently licensed COVID-19 vaccines share in common that they require refrigeration to maintain their potency and depend on a functioning cold-chain (Nachega et l. Lancet Glob. Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys Health 9, e746-e748). This renders distribution and storage of the vaccines challenging, especially in areas with limited access to refrigeration, which includes most developing countries with often remote or impoverished regions. Therefore, developing thermostable vaccines, which do not require refrigeration, would greatly simplify the distribution and storage of the vaccines and would increase accessibility to the vaccines globally. Globally escalating infection rates and the emergence of highly transmissible Variants of Concern (VOCs) leading to reinfections and breakthrough infections, evidence the limitations of current mRNA-based or adenovirus vectored vaccines or monoclonal antibody treatments, and the need for new vaccines and treatments with the reach to achieve a global solution to this global crisis. There are numerous further potential infection threats to human health needing improved vaccines and treatments, especially in terms of high efficacy in binding of immunological entities to the targeted antigen. WO 2017/167988 A1 discloses a synthetic, self-assembling multiepitope display nanoparticle platform (called “ADDomer”) based on adenovirus penton base polypeptides for highly efficient vaccination by genetically encoded multiepitope display. WO 2020/025724 A1 discloses further adenovirus penton base-derived polypeptide scaffolds for optimized presentation of oligopeptides, polypeptide sequences, protein domains, proteins and/or protein complexes made up of two, several or many subunits, in particular for vaccination purposes. WO 2021/156489 A1 discloses further engineered polypeptides derived from adenovirus penton base proteins capable of forming scaffolds for optimized presentation of peptidic entities such as oligopeptides, polypeptide sequences, protein domains, proteins and protein complexes made up of two, several or many subunits, preferably as high affinity agents to target molecules. The technical problem underlying the present invention is the provision of further improved adenovirus penton base protein-related tools for treatment or prevention of infectious and other diseases. In particular, the present invention provides an adenovirus penton-based polypeptide assembly comprising (i) at least one pentamer of adenovirus penton base protomer Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys polypeptides each having an adenovirus fiber protein binding cleft and (ii) at least one polypeptide comprising (1) at least one adenovirus fiber protein N-terminal fragment specifically binding to the adenovirus fiber protein binding cleft of said penton base protomers, (2) a multimerization domain and (3a) a non-adenoviral peptide component and/or (3b) a drug or label covalently or non-covalently coupled to the multimerization domain or the non-adenoviral peptide. Preferably, the polypeptide assembly according to the invention further comprises one or more linkers between (sub-)components (1) and (2) and/or (2) and (3a) and/or (2) and (3a) and/or (3a) and (3b) of component (ii). The binding of (sub-)component (1) of component (ii) to component (i) at the adenovirus fiber protein binding cleft may covalently established for example, by introducing suitable coupling residues in the binding cleft of component (i) and in (sub-)component (1). Component (i) may also contain suitable coupling residues for enabling and/or stabilizing VLP-forming capacity of component (i). In other embodiments of the invention, binding of (sub-)component (1) of component (ii) to component (i) at the adenovirus fiber protein binding cleft may be established by non-covalent interaction (as is the case in the naturally occurring binding of the adenovirus fiber protein to an adenovirus fiber binding cleft). The term "adenovirus penton base protomer polypeptide" as used in the context of the present invention refers to an adenoviral protein that assembles into the so called "penton base". Each penton base comprises five penton base protomer polypeptides. The adenovirus penton base protomer polypeptide is one of three proteins forming the adenoviruses coat. The other proteins are hexon and fiber. Adenovirus penton base protomer polypeptides useful in the present invention originate from adenovirus specific to any mammalian species. Preferably the adenovirus is a human or a non-human great ape adenovirus, preferably Chimpanzee (Pan), Gorilla (Gorilla) and orangutans (Pongo), more preferably Bonobo (Pan paniscus) and common Chimpanzee (Pan troglodytes). It is understood by the skilled person that the penton base proteins of different adenovirus will vary in their amino acid sequence, but all such naturally occurring variants are encompassed by the term "adenovirus penton base protomer polypeptide". Additionally, the term encompasses artificial variants, in particular mutants, that comprise insertions, deletions and/or substitutions of one or more amino acids in comparison to the naturally occurring (i.e., wildtype) penton base protomer polypeptide sequence. Examples for artificial mutants or variants, respectively, useful in the present invention comprise modifications of the N-terminal domain, V loop, first RGD, second RGD loop and/or adenovirus fiber binding cleft, e.g. as specifically described in WO Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys 2017/167988 A1 as well as disclosed herein. Mutations in variants of adenovirus penton base protomer polypeptides particularly useful in the present invention may comprise insertions, substitutions and/or deletions of one or more amino acids in other parts of the adenovirus penton base protomer polypeptide instead of or in addition to, respectively, the modifications of the N-terminal domain, V loop, first RGD, second RGD loop and/or adenovirus fiber binding cleft. Preferably, any such artificial variants are useful and comprized, respectively, in the present invention as long as the artificially modified adenovirus penton base protomer polypeptide assembles into penton subunits and 12 of these assemble into VLPs. Preferably, the artificial variants have at least 75%, more preferably at least 80%, more preferably at least 85%, more preferably at least 90%, more preferably at least 92%, more preferably at least 94%, more preferably at least 96%, more preferably 98%, more preferably 99 % sequence identity to a naturally occurring (i.e., wildtype) adenovirus penton base protomer polypeptide. Particularly preferred mutants or variant, respectively, of the adenovirus penton protomer polypeptides for use in the invention, differing in sequence from naturally occurring (i.e., wildtype) penton base proteins by amino acid insertions, deletions and substitutions as well as preferred wildtype adenovirus penton protomer polypeptides are outlined in more detail below. The term "coupling residue" as used in the context of the present invention refers to a natural or non-naturally occurring amino acid that has a side chain capable of forming a covalent bond. Coupling residues can be inserted into a polypeptide of the present invention. If the coupling residue is a naturally occurring amino acid that is encoded by DNA the insertion of a coupling residue merely requires the modification of the DNA that is directing expression of the polypeptide of the invention e.g., insertion of a codon that encodes such amino acid or mutation of an existing codon. Preferred examples of naturally occurring amino acids that are coupling residues within the meaning of this term are Asp, Glu, Lys and Cys. Cys is particularly preferred since it will form a disulfide bond with another Cys depending on the redox status of the environment. Especially the latter allows the formation of a stable interconnection between two separate polypeptides. A "linker" in the context of the present invention refers to any chemical moiety that is flexible and sterically separates two chemical moieties such as the components/sub-components used in the assembly of the present invention as outlined above. Preferred linkers are moieties having a length to width ratio of at least 10:1, preferably of at least 20:1, more preferably of at least 50:1. Preferably, linkers are linear molecules. It is preferred that the two moieties linked by a linker are covalently or non-covalently, preferably covalently attached to the respective ends of the linker. Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys A "peptide linker" in the context of the present invention refers to an amino acid sequence, i.e. an oligopeptide or polypeptide, which sterically separates two parts within the engineered polypeptides of the present invention. Typically, such linker comprises or consists of, respectively 2 to 100, preferably 3 to 50, more preferably 5 to 20 amino acids. Thus, such linkers have a minimum length of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 amino acids, and a maximum length of at least 100, 95, 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, or 15 amino acids or less. Peptide linkers may also provide flexibility among the two parts that are linked together. Such flexibility is generally increased, if the amino acids are small. Accordingly, flexible peptide linkers comprise an increased content of small amino acids, in particular of glycines and/or alanines, and/or hydrophilic amino acids such as serines, threonins, asparagines and glutamines. Preferably, more than 20%, more than 30%, mor than 40%, more than 50%, or more than 60% of the amino acids of the peptide linker are small amino acids. Preferred linkers for use in the present invention comprise or consist of, respectively, one or more Gly residue(s) such as linkers having the general formula -(G)m- with m being an integer of at least 1, preferably 1 to 30, more preferably 2 to 20, more preferably 2 to 10, particularly preferred -GG-, -GGG-, GGGG-, or -GGGGG-. Further preferred linkers comprise or consist of, respectively, one or more Ser residue(s) such as linkers of the general formula -(S)n- with n being an integer of at least 1, preferably 1 to 30, more preferably 2 to 20, more preferably 2 to 10, particularly preferred -SS-, -SSS-, -SSSS-, or -SSSSS-. Other preferred linkers comprise one or more Gly residue(s) and one or more Ser residue(s). Yet further preferred linkers consist of one or more Gly residue(s) and one or more Ser residue(s). Preferred examples include linkers of the general formula -GmSn- with m and n independently representing an integer of at least 1, preferably 1 to 20, more preferably 2 to 20, more preferably 2-10, such as linkers -GS-, -GGS-, -GGGS-, wherein it is to be understood that the G and S residues in such linkers may be arranged in any sequence. The multimerization domain of the polypeptide assembly of the invention may be selected from dimerization domains, trimerization domains, tetramerization domains and pentamerization domains. Dimerization, trimerization and pentamerization domains are particularly preferred. Preferred multimerization domains comprise an alpha-helical coiled- coil structure which may be derived from or be, respectively, natural coiled-coil sequences, or may be synthetic coiled-coil sequences. In a preferred embodiment these can comprise synthetic or natural alpha-helical coiled coil dimerization, trimerization, tetramerization or pentamerization domains including, but not limited to, dimerization, trimerization, Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys tetramerization or pentamerization comprising or consisting of, respectively, of a motif laid down in the Protein Data Bank (PDB). Preferred examples of dimerization domains for use in the invention include, but are not limited to, dimerization domains comprising or essentially consisting of or consisting of, respectively, a motif such as PDB identifiers 1P9I, 4BWD, 1T6F, 1U0I or 5C9N. Preferred examples of trimerization domains for use in the invention include, but are not limited to, trimerization domains comprising or essentially consisting of or consisting of, respectively, a motif such as PDB identifiers 1COI, 3LT7, 3H7Z, 4DZK, 4DZL or 3LT6. Preferred examples of tetramerization domains for use in the invention include, but are not limited to, tetramerization domains comprising or essentially consisting of or consisting of, respectively, a motif such as PDB identifiers 1FE6, 3R4H or 1YOD. Preferred examples of pentamerization domains for use in the invention include, but are not limited to, pentamerization domains comprising or essentially consisting of or consisting of, respectively, a motif such as PDB identifiers 4PN8 and 4PND. The multimerization domain may also be selected from non-alpha helical coiled-coil domains such as a T4 foldon trimerization domain, preferably comprising or consisting of PBD identifier 1 RFO. The term "non-adenoviral peptide component" refers to an amino acid sequence that has no sequence identity to any polypeptide present in an adenovirus, in particular in naturally occurring adenovirus penton base protomers over a length of at least 5 amino acids. Preferably, the non-adenoviral peptide component has no sequence identity to any polypeptide present in adenovirus over a stretch of at least 10, preferably at least 15 amino acids. The non-adenoviral peptide component may preferably be selected from non- adenoviral oligonucleotides, polypeptides, proteins and/or protein complexes. Preferred non-adenoviral peptide components include, but are not limited to, target-specific binding domains or target specific binding sequences such antigens, antibodies, antibody mimetics and antibody fragments. The term "target specific binding domain" as used herein refers to a polypeptide which facilitates specific binding to a target. The binding of such a target specific binding domain is considered specific to a given target if it binds with the highest affinity to the respective target and only with lower affinity such as at least 10fold lower, preferably at least 100fold lower affinity to other targets even to targets with a related amino acid sequence. The term "target" as used herein refers to a natural existing cellular or molecular structure towards which molecules have a certain binding affinity or to which molecules specifically Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys bind. A target may comprise one or more epitopes. In the context of the present invention target specific binding domains are preferably antigens and antibodies (wherein it is understood that “antibody” in this context refers to any antigen-binding antibody, antibody fragment or antibody mimetic). As regards antibody-antigen interaction, the “target” of an antigen is typically an antibody directed to the antigen, whereas it is understood that the target of an antibody (or antibody fragment or mimetic thereof) is an antigen to which the antibody. (or antibody fragment or mimetic thereof) binds specifically. The term "antigen" as used in the context of the present invention refers to any structure recognized by molecules of the immune response such as e.g., antibodies, T cell receptors (TCRs) and the like. An antigen may be foreign or toxic to the body or may be a cellular protein that is associated with a particular disease. Antigens are recognized by highly variable antigen receptors (B-cell receptor or T-cell receptor) of the adaptive immune system and may elicit a humoral or cellular immune response. Antigens that elicit such a response are also referred to as immunogens. A fraction of the proteins inside cells, irrespective of whether they are foreign or cellular, are processed into smaller peptides and presented to by the major histocompatibility complex (MHC). A cellular immune response is elicited, if the small peptide fragment is bound by a T-cell receptor. Cell surface antigens can be selected from the group of cytokine receptors, integrins, cell adhesion molecules, cell type-specific cell surface antigens, tissue-specific cell surface antigens, tumor-associated antigens (also denoted herein simply as “tumor antigens), preferably cell surface-expressed tumor- associated antigens, cluster of differentiation antigens, or carbohydrates. The term "specific binding" as used in the context of the present invention means that a binding moiety (e.g. an antibody) binds stronger to a target, such as an epitope, for which it is specific compared to the binding to another target if it binds to the first target with a dissociation constant (Kd) which is lower than the dissociation constant for the second target. Targets can be recognized by their ligands which bind with a certain affinity to their targets and thus, the ligand binding to its respective target results in a biological effect. Preferably, the binding is both specific and occurs with a high affinity, preferably with a Kd of equal or even less than 10 ^-7 , 10 ^-8 , 10 ^-9 , 10 ^-10 M or less. Such affinity is preferably measured at 37°C Suitable assays include surface plasmon resonance measurements (e.g. Biacore), quartz crystal microbalance measurements (e.g. Attana), competition assays and the like. Antigens may be, for example, viral antigens, bacterial antigens, protozoan antigens, fungal antigens and tumor antigens. Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys Preferred viral antigens include, but are not limited to coronavirus antigens, influenza virus antigens, respiratory syncitial virus (RSV) antigens, ebola virus antigens, Chikungunya virus antigens, Zika virus antigens, Dengue virus antigens, measles virus antigens, human papillomavirus antigens, Gumboro virus antigens and Newcastle virus antigens. Preferred RSV antigens are selected from Gcc epitopes (also referred to “Gcc antigens”). Preferred Gcc epitopes of RSV are selected Gcc epitopes from subgroup A (also denoted as “Gacc”) and Gcc epitopes from subgroups B (also denoted as “Gbcc”). RSV antigens such as Gcc eptiopes can also be included into the polypeptides and assemblies, respectively, of the invention as oligomers or concatemers of such Gcc epitopes. One or more Gcc epitopes may also fused to a foldon tag, preferably a dimer of Gcc epitopes, preferably selected from Gacc and Gbcc, preferably fused C-terminally to a foldon tag. Highly preferred Gcc antigens are peptide sequences comprising, essentially consisting of, or consisting of one or more the following: Gacc: GSSGSSEEEGGSRQNKPPNKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKEEE (SEQ ID NO: 55) Gcc concatemer (four Gcc peptides in thr order of Gcc A2, Gcc B1, Gcc A2 and GccB1 fused together via glutamate-rich linkers): MEESEESGGRQNKPPSKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKEEEEESEES RKNPPKKP KDDYHFEVFNFVPCSICGNNQLCKSICKTIPNKKEESEESGGRQNKPPSKPNNDFHFEVF NFVPCSIC SNNPTCWAICKRIPNKEEEEESEESRKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSIC KTIPNKKE ESEESGG (SEQ ID NO: 56) Gcc foldon (dimer of a Gacc and a Gbcc followed C-terminally by a foldon tag) MEESEESGGRKNPPKKPKDDYHFEVFNFVPCSICGNNQLCKSICKTIPNKKEEEEESEES GGRQNKPP SKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKEEESSGGSGGGGSGGGGSGGGGS GSSAIGGY IPEAPRDGQAYVRKDGEWVLLSTFLGSGLEVLFQGPLE (SEQ ID NO: 57) Preferred coronavirus antigens are selected from antigens of SARS-CoV, SARS-CoV-2 and MERS-CoV. Preferred SARS-CoV-2 antigens are antigenic sequences of the receptor binding domain (RBD) of a SARS-CoV-2, more preferably the antigen is selected from receptor binding motifs (RBM) of a SARS-CoV-2. Included therein are also consensus sequences at least potentially covering more than one SARS-CoV-2 RBMs. More preferably, the RBM is an RBM of a SARS-CoV-2 variant of concern (VoC). Particularly preferred examples of SARS- Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys CoV-2 antigens include, but are not limited to, SARS-CoV-2 Wuhan RBM, VoC Alpha RBM, VoC Beta RBM, VoC Delta RBM and VoC Omicron RBM and sub-strains thereof including, but not limited to, Omicron BA4, BA5, BA27 and others. Particularly preferred SARS-CoV-2 antigens comprise, essentially consist of or consist of, respectively, one ore more of the sequences according to SEQ ID NO: 53, 54, 60 and 61, whereby it is understood that the antigen or epitope may comprise, essentially consist of or consist of, respectively, oligomers such as dimers, tirmers quardruples, of these sequences, or partial sequences of these sequences, preferably as long as such partial sequences provide or at least contribute to the antigenicity. The term "antibody" as used in the context of the present invention refers to glycoproteins belonging to the immunoglobulin superfamily. The terms antibody and immunoglobulin are often used interchangeably. An antibody refers to a protein molecule produced by plasma cells and is used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the (typically foreign) target, its antigen. The term "antibody fragment" as used herein, refers to one or more fragments of an antibody that retain the ability to specifically bind to an antigen. Examples of binding fragments encompassed within the term "antibody fragment" include a fragment antigen binding (Fab) fragment, a Fab' fragment, a F(ab')2 fragment, a heavy chain antibody, a single-domain antibody (sdAb), a single-chain fragment variable (scFv), a fragment variable (Fv), a VH domain, a VL domain, a single domain antibody, a nanobody, an IgNAR (immunoglobulin new antigen receptor), a di-scFv, a bispecific T-cell engager (BITEs), a dual affinity re- targeting (DART) molecule, a triple body, a diabody, a single-chain diabody, an alternative scaffold protein, and a fusion protein thereof. As used herein, the term “antibody fragment” also includes cameloid antibodies and antibodies of cartilaginous fish. The term "diabody" as used herein is comprized within the term “antibody” and refers to a fusion protein or a bivalent antibody which can bind different antigens. A diabody is composed of two single protein chains which comprise fragments of an antibody, namely variable fragments. Diabodies comprise a heavy chain variable domain (VH) connected to a light-chain variable domain (VL) on the same polypeptide chain (VH-VL, or VL-VH). By using a short peptide connecting the two variable domains, the domains are forced to pair with the complementary domain of another chain and thus, create two antigen-binding sites. Diabodies can target the same (monospecific) or different antigens (bispecific). Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys The term "single domain antibody" as used in the context of the present invention refers to antibody fragments consisting of a single, monomeric variable domain of an antibody. Simply, they only comprise the monomeric heavy chain variable regions of heavy chain antibodies produced by camelids or cartilaginous fish. Due to their different origins, they are also referred to VHH or VNAR (variable new antigen receptor)-fragments. Alternatively, single-domain antibodies can be obtained by monomerization of variable domains of conventional mouse or human antibodies by the use of genetic engineering. They show a molecular mass of approximately 12-15 kDa and thus, are the smallest antibody fragments capable of antigen recognition. Further examples include nanobodies or nanoantibodies. The term "antibody mimetic" as used in the context of the present invention refers to compounds which can specifically bind antigens, similar to an antibody, but are not structurally related to antibodies. Usually, antibody mimetics are artificial peptides or proteins with a molar mass of about 3 to 20 kDa which comprise one, two or more exposed domains specifically binding to an antigen. Examples include inter alia the LACI-D1 (lipoprotein- associated coagulation inhibitor); affilins, e.g. human-γ B crystalline or human ubiquitin; cystatin; Sac7D from Sulfolobus acidocaldarius; lipocalin and anticalins derived from lipocalins; DARPins (designed ankyrin repeat domains); SH3 domain of Fyn; Kunits domain of protease inhibitors; monobodies, e.g. the 10th type III domain of fibronectin; adnectins: knottins (cysteine knot miniproteins); atrimers; evibodies, e.g. CTLA4-based binders, affibodies, e.g. three-helix bundle from Z-domain of protein A from Staphylococcus aureus; Trans-bodies, e.g. human transferrin; tetranectins, e.g. monomeric or trimeric human C-type lectin domain; microbodies, e.g. trypsin-inhibitor-II; affilins; armadillo repeat proteins. Nucleic acids and small molecules are sometimes considered antibody mimetics as well (aptamers), but not artificial antibodies, antibody fragments and fusion proteins composed from these. Common advantages over antibodies are better solubility, tissue penetration, stability towards heat and enzymes, and comparatively low production costs. As used herein, the term "Kd" (usually measured in "mol/L", sometimes abbreviated as "M") is intended to refer to the dissociation equilibrium constant of the particular interaction between a binding moiety (e.g. an antibody or fragment thereof) and a target molecule (e.g. an antigen or epitope thereof). Methods for determining Kd include, without limitation, ELISA and surface plasmon resonance assays. The term "epitope", also known as antigenic determinant, as used in the context of the present invention is the part of a macromolecule that is recognized by the immune system, specifically by antibodies, B cells, or T cells. As used herein, an "epitope" is the part of a Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys macromolecule capable of binding to an antibody (e.g. an antibody or antigen-binding fragment thereof) as described herein. Epitopes usually consist of chemically active surface groupings of molecules such as amino acids or sugar side chains and usually have specific three-dimensional structural characteristics, as well as specific charge characteristics. Conformational and non- conformational epitopes can be distinguished in that the binding to the former but not the latter is lost in the presence of denaturing solvents. As used herein, a "conformational epitope" refers to an epitope of a linear macromolecule (e.g. a polypeptide) that is formed by the three-dimensional structure of said macromolecule. In the context of the present application, a "conformational epitope" is a "discontinuous epitope", i.e. the conformational epitope on the macromolecule (e.g. a polypeptide) which is formed from at least two separate regions in the primary sequence of the macromolecule (e.g. the amino acid sequence of a polypeptide). In other words, an epitope is considered to be a "conformational epitope" in the context of the present invention, if the epitope consists of at least two separate regions in the primary sequence to which an antibody (or an antigen- binding fragment thereof) binds simultaneously, wherein these at least two separate regions are interrupted by one or more regions in the primary sequence to which an antibody (or an antigen-binding fragment thereof) does not bind. Preferably, such a "conformational epitope" is present on a polypeptide, and the two separate regions in the primary sequence are two separate amino acid sequences to which an antibody (or an antigen-binding fragment thereof) binds, wherein these at least two separate amino acid sequences are interrupted by one more amino acid sequences in the primary sequence to which an antibody (or an antigen-binding fragment thereof) does not bind. Preferably, the interrupting amino acid sequence is a contiguous amino acid sequence comprising two or more amino acids to which the antibody (or the antigen-binding fragment thereof) does not bind. The at least two separate amino acid sequences to which an antibody of the invention (or an antigen-binding fragment thereof) binds are not particularly limited regarding their length. Such a separate amino acid sequence may consist of only one amino acid as long as the total number of amino acids within said at least two separate amino acid sequences is sufficiently large to effect specific binding between the antibody (or the antigen- binding fragment thereof) and the conformational epitope. Preferably, the antibody or antibody fragment is directed against an antigen as outlined above. The term "label" as used in the context of the present invention refers to any kind of compound being suitable for diagnostic purposes. Preferred compounds are selected from a Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys fluorescent dye, a radioisotope and a contrast agent. A contrast agent is a dye or other substance that helps to show abnormal areas inside the body. In one embodiment the term label refers to a compound that comprises a chelating agent which forms a complex with divalent or trivalent metal cations. Preferred radioisotopes/fluorescence emitting isotopes are selected from the group consisting of alpha radiation emitting isotopes, gamma radiation emitting isotopes, Auger electron emitting isotopes, X-ray emitting isotopes, fluorescence emitting isotopes, such as ¹⁸ F, ⁵¹ Cr, ⁶⁷ Ga, ⁶⁸ Ga, ¹¹⁵ In, ⁹⁹ Tc, ¹⁴⁰ La, ¹⁷⁵ Yb, ¹⁵³ Sm, 1 ⁶⁶ Ho, ⁸⁸ Y, ⁹⁰ Y, ¹⁴⁹ Pm, ¹⁷⁷ Lu, ⁴⁷ Sc, ¹⁴² Pr, ¹⁵⁹ Gd, ²¹² Bi, ⁷² As, ⁷⁹ Se, ⁹⁷ Ru, ¹⁰⁹ Pd, ¹⁸⁷ Rh, ¹¹⁹ Sb, ¹²⁸ Ba, ¹²³ I, ¹²⁴ I, ¹³¹ I, ¹⁹⁷ Hg, ²¹¹ At, ¹⁶⁹ Eu, ²⁰³ Pb, ²¹² Pb, ⁶⁴ Cu, ⁶⁷ Cu, ¹⁸⁸ Re, ¹⁸⁶ Re, ¹⁹⁸ Au and ¹⁹⁹ Ag. Preferred fluorescent dyes are selected from the following classes of dyes: Xanthens (e.g. Fluorescein), Acridines (e.g. Acridine Yellow), Oxazines (e.g. Oxazine 1), Cynines (e.g. Cy7 / Cy 3), Styryl dyes (e.g. Dye- 28), Coumarines (e.g. Alexa Fluor 350), Porphines (e.g. Chlorophyll B), Metal-Ligand- Complexes (e.g. PtOEPK), Fluorescent proteins (e.g APC, R- Phycoerythrin), Nanocrystals (e.g QuantumDot 705), Perylenes (e.g. Lumogen Red F300) and Phtalocyanines (e.g. IRDYE™700DX) as well as conjugates and combinations of these classes of dyes. Preferred contrast agents are selected from paramagnetic agents, e.g. Gd, Eu, W and Mn, preferably complexed with a chelating agent. Further options are supramagnetic iron (Fe) complexes and particles, compounds containing atoms of high atomic number, i.e. iodine for computer tomography (CT), microbubbles and carriers such as liposomes that contain these contrast agents. The term "drug" is to be understood in the context of the present invention in its broadest sense to refer to any compound that elicits a prophylactic, therapeutic or palliative effect in a patient. Preferably, it is a small molecule e.g., having a molecular size of below 500 Da. Preferably, the polypeptide assembly according to the invention comprises 12 pentamers of component (i) and 1 to 12 multimers of component (ii) said multimers being selected from dimers, trimers, tetramers and pentamers. An assembly of the invention comprising 12 pentamers of component (i) is also denoted as a VLP of the invention. According to the invention, component(s) (ii) may be bound to component(s) (i) by covalent or non-covalent interaction. Preferred penton base protomer polypeptides for use in the invention are or are derived from, respectively, adenovirus penton base protomers of human adenovirus serotype 2 (hAd2), human adenovirus serotype 3 (hAd3), human adenovirus serotype 4 (hAd4), human adenovirus serotype 5 (hAd5), human adenovirus serotype 7 (hAd7), human adenovirus serotype 9 (hAd9), human adenovirus serotype 11 (hAd11), human adenovirus serotype 12 Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys (hAd12), human adenovirus serotype 15 (hAd15), human adenovirus serotype 17 (hAd17), human adenovirus serotype 25 (hAd25), human adenovirus serotype 35 (hAd35), human adenovirus serotype 37 (hAd37), human adenovirus serotype 41 (hAd41), human adenovirus serotype 49 (hAd49), gorilla adenovirus (GorAd), chimpanzee adenovirus serotype Y25 (ChAdY25), chimpanzee adenovirus serotype 3 (ChAd3), chimpanzee adenovirus serotype 4 (ChAd4), chimpanzee adenovirus serotype 5 (ChAd5), chimpanzee adenovirus serotype 6 (ChAd6), chimpanzee adenovirus serotype 7 (ChAd7), chimpanzee adenovirus serotype 8 (ChAd8), chimpanzee adenovirus serotype 9 (ChAd9), chimpanzee adenovirus serotype 10 (ChAd10), chimpanzee adenovirus serotype 11 (ChAd11), chimpanzee adenovirus serotype 12 (ChAd12), chimpanzee adenovirus serotype 17 (ChAd17), chimpanzee adenovirus serotype 19 (ChAd19), chimpanzee adenovirus serotype 20 (ChAd20), chimpanzee adenovirus serotype 22 (ChAd22), chimpanzee adenovirus serotype 24 (ChAd24), chimpanzee adenovirus serotype 26 (ChAd26), chimpanzee adenovirus serotype 30 (ChAd30), chimpanzee adenovirus serotype 31 (ChAd31), chimpanzee adenovirus serotype 37 (ChAd37), chimpanzee adenovirus serotype 38 (ChAd38), chimpanzee adenovirus serotype 44 (ChAd44), chimpanzee adenovirus serotype 63 (ChAd63), chimpanzee adenovirus serotype 82 (ChAd82), pan adenovirus serotype 1 (PanAd1), pan adenovirus serotype 2 (PanAd2), pan adenovirus serotype 3 (PanAd3), chimpanzee adenovirus serotype 55 (ChAd55), chimpanzee adenovirus serotype 73 (ChAd73), chimpanzee adenovirus serotype 83 (ChAd83), chimpanzee adenovirus serotype 146 (ChAd146), chimpanzee adenovirus serotype 147 (ChAd147), simian adenovirus serotype 18 (sAd18), simian adenovirus serotype 20 (sAd20), simian adenovirus serotype 49 (sAd49), rhesus adenovirus serotype 51 (rhAd51), rhesus adenovirus serotype 52 (rhAd52) and/or rhesus adenovirus serotype 53 (rhAd53). Preferred amino acid sequences of the above-indicated adenovirus penton protomer are laid down in generally accessible databases such as UniProt, UniProtE and GenBank, and especially preferred sequences referred to herein for the above-mentioned adenovirus subtypes are laid down in UniProt Acc. No. Q2Y0H9 (human adenovirus serotype 3; SEQ ID NO: 1), UniProt Acc. No. P03276 (human adenovirus serotype 2; SEQ ID NO: 2), UniProt Acc. No. Q2KSF3 (human adenovirus serotype 4; SEQ ID NO: 3), UniProt Acc. No. P12538 (human adenovirus serotype 5; SEQ ID NO: 4), UniProt Acc. No. Q9JFT6 (human adenovirus serotype 7; SEQ ID NO: 5), UniProt Acc. No. Q5TJ09, (human adenovirus serotype 9; SEQ ID NO: 6), UniProt Acc. No. D2DM93 (human adenovirus serotype 11; SEQ ID NO: 7), UniProt Acc. No. P36716 (human adenovirus serotype 12; SEQ ID NO: 8), UniProt Acc. No. E1CIJ8 (human adenovirus serotype 15; SEQ ID NO: 9), UniProt Acc. No. F1DT65 (human adenovirus serotype 17; SEQ ID NO: 10), UniProt Acc. No. M0QUK0 Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys (human adenovirus serotype 25; SEQ ID NO: 11), UniProt Acc. No. Q7T941 (human adenovirus serotype 35; SEQ ID NO: 12), UniProt Acc. No. Q912J1 (human adenovirus serotype 37; SEQ ID NO: 13), UniProt Acc. No. F8WQN4 (human adenovirus serotype 41; SEQ ID NO: 14), GenBank Acc. No. ABD52391.1 (human adenovirus serotype 49) UniProt Acc. No. E5L3Q9 (gorilla adenovirus; SEQ ID NO: 15), UniProt Acc. No. G9G849 (chimpanzee adenovirus; SEQ ID NO: 16), UniProt Acc. No. H8PFZ9 (simian adenovirus serotype 18; SEQ ID NO: 17), UniProt Acc. No. F6KSU4 (simian adenovirus serotype 20; SEQ ID NO: 18), UniProt Acc. No. F2WTK5 (simian adenovirus serotype 49; SEQ ID NO: 19), UniProt Acc. No. A0A0A1EWW1 (rhesus adenovirus serotype 51; SEQ ID NO: 20), UniProt Acc. No. A0A0A1EWX7 (rhesus adenovirus serotype 52; SEQ ID NO: 21), and UniProt Acc. No. A0A0A1EWZ7 (rhesus adenovirus serotype 53; SEQ ID NO: 22). The amino acid sequences of the above penton base protoemers are as follows (the respective UniProt Acc. No. or GenBank Acc. No. is indicated in brackets): Human Adenvirus Serotype 3 penton base hAd3 (UniProt Acc. No. Q2Y0H9); SEQ ID NO: 1: MRRRAVLGGA VVYPEGPPPS YESVMQQQAA MIQPPLEAPF VPPRYLAPTE GRNSIRYSEL SPLYDTTKLY LVDNKSADIA SLNYQNDHSN FLTTVVQNND FTPTEASTQT INFDERSRWG GQLKTIMHTN MPNVNEYMFS NKFKARVMVS RKAPEGVTVN DTYDHKEDIL KYEWFEFILP EGNFSATMTI DLMNNAIIDN YLEIGRQNGV LESDIGVKFD TRNFRLGWDP ETKLIMPGVY TYEAFHPDIV LLPGCGVDFT ESRLSNLLGI RKRHPFQEGF KIMYEDLEGG NIPALLDVTA YEESKKDTTT ETTTLAVAEE TSEDDDITRG DTYITEKQKR EAAAAEVKKE LKIQPLEKDS KSRSYNVLED KINTAYRSWY LSYNYGNPEK GIRSWTLLTT SDVTCGAEQV YWSLPDMMQD PVTFRSTRQV NNYPVVGAEL MPVFSKSFYN EQAVYSQQLR QATSLTHVFN RFPENQILIR PPAPTITTVS ENVPALTDHG TLPLRSSIRG VQRVTVTDAR RRTCPYVYKA LGIVAPRVLS SRTF hAd2 (UniProt Acc. No. P03276); SEQ ID NO: 2: MQRAAMYEEG PPPSYESVVS AAPVAAALGS PFDAPLDPPF VPPRYLRPTG GRNSIRYSEL APLFDTTRVY LVDNKSTDVA SLNYQNDHSN FLTTVIQNND YSPGEASTQT INLDDRSHWG GDLKTILHTN MPNVNEFMFT NKFKARVMVS RSLTKDKQVE LKYEWVEFTL PEGNYSETMT IDLMNNAIVE HYLKVGRQNG VLESDIGVKF DTRNFRLGFD PVTGLVMPGV YTNEAFHPDI ILLPGCGVDF THSRLSNLLG IRKRQPFQEG FRITYDDLEG GNIPALLDVD AYQASLKDDT Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys EQGGDGAGGG NNSGSGAEEN SNAAAAAMQP VEDMNDHAIR GDTFATRAEE KRAEAEAAAE AAAPAAQPEV EKPQKKPVIK PLTEDSKKRS YNLISNDSTF TQYRSWYLAY NYGDPQTGIR SWTLLCTPDV TCGSEQVYWS LPDMMQDPVT FRSTSQISNF PVVGAELLPV HSKSFYNDQA VYSQLIRQFT SLTHVFNRFP ENQILARPPA PTITTVSENV PALTDHGTLP LRNSIGGVQR VTITDARRRT CPYVYKALGI VSPRVLSSRT F hAd4 (UniProt Acc. No. Q2KSF3); SEQ ID NO: 3: MMRRAYPEGP PPSYESVMQQ AMAAAAAIQP PLEAPYVPPR YLAPTEGRNS IRYSELTPLY DTTRLYLVDN KSADIASLNY QNDHSNFLTT VVQNNDFTPT EASTQTINFD ERSRWGGQLK TIMHTNMPNV NQFMYSNKFK ARVMVSRKTP NGVTVGDNYD GSQDELKYEW VEFELPEGNF SVTMTIDLMN NAIIDNYLAV GRQNGVLESD IGVKFDTRNF RLGWDPVTEL VMPGVYTNEA FHPDIVLLPG CGVDFTESRL SNLLGIRKRQ PFQEGFQIMY EDLDGGNIPA LLDVEAYEKS KEESVAAATT AVATASTEVR DDNFASAAAV AAVKADETKS KIVIQPVEKD SKERSYNVLS DKKNTAYRSW YLAYNYGDRD KGVRSWTLLT TSDVTCGVEQ VYWSLPDMMQ DPVTFRSTHQ VSNYPVVGAE LLPVYSKSFF NEQAVYSQQL RAFTSLTHVF NRFPENQILV RPPAPTITTV SENVPALTDH GTLPLRSSIR GVQRVTVTDA RRRTCPYVYK ALGIVAPRVL SSRTF hAd5 (UniProt Acc. No. P12538); SEQ ID NO: 4: MRRAAMYEEG PPPSYESVVS AAPVAAALGS PFDAPLDPPF VPPRYLRPTG GRNSIRYSEL APLFDTTRVY LVDNKSTDVA SLNYQNDHSN FLTTVIQNND YSPGEASTQT INLDDRSHWG GDLKTILHTN MPNVNEFMFT NKFKARVMVS RLPTKDNQVE LKYEWVEFTL PEGNYSETMT IDLMNNAIVE HYLKVGRQNG VLESDIGVKF DTRNFRLGFD PVTGLVMPGV YTNEAFHPDI ILLPGCGVDF THSRLSNLLG IRKRQPFQEG FRITYDDLEG GNIPALLDVD AYQASLKDDT EQGGGGAGGS NSSGSGAEEN SNAAAAAMQP VEDMNDHAIR GDTFATRAEE KRAEAEAAAE AAAPAAQPEV EKPQKKPVIK PLTEDSKKRS YNLISNDSTF TQYRSWYLAY NYGDPQTGIR SWTLLCTPDV TCGSEQVYWS LPDMMQDPVT FRSTRQISNF PVVGAELLPV HSKSFYNDQA VYSQLIRQFT SLTHVFNRFP ENQILARPPA PTITTVSENV PALTDHGTLP LRNSIGGVQR VTITDARRRT Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys CPYVYKALGI VSPRVLSSRT F hAd7 (UniProt Acc. No. Q9JFT6); SEQ ID NO: 5: MRRRAVLGGA MVYPEGPPPS YESVMQQQAA MIQPPLEAPF VPPRYLAPTE GRNSIRYSEL SPLYDTTKLY LVDNKSADIA SLNYQNDHSN FLTTVVQNND FTPTEASTQT INFDERSRWG GQLKTIMHTN MPNVNEYMFS NKFKARVMVS RKAPEGVIVN DTYDHKEDIL KYEWFEFTLP EGNFSATMTI DLMNNAIIDN YLEIGRQNGV LESDIGVKFD TRNFRLGWDP ETKLIMPGVY TYEAFHPDIV LLPGCGVDFT ESRLSNLLGI RKRHPFQEGF KIMYEDLEGG NIPALLDVTA YEESKKDTTT ETTTLAVAEE TSEDDNITRG DTYITEKQKR EAAAAEVKKE LKIQPLEKDS KSRSYNVLED KINTAYRSWY LSYNYGNPEK GIRSWTLLTT SDVTCGAEQV YWSLPDMMQD PVTFRSTRQV NNYPVVGAEL MPVFSKSFYN EQAVYSQQLR QATSLTHVFN RFPENQILIR PPAPTITTVS ENVPALTDHG TLPLRSSIRG VQRVTVTDAR RRTCPYVYKA LGIVAPRVLS SRTF hAd9 ( UniProt Acc. No.Q5TJ09); SEQ ID NO: 6: MRRAVVSSSP PPSYESVMAQ ATLEVPFVPP RYMAPTEGRN SIRYSELAPQ YDTTRVYLVD NKSADIASLN YQNDHSNFLT TVVQNNDFTP AEASTQTINF DERSRWGGDL KTILHTNMPN VNEYMFTSKF KARVMVARKH PEGVVETDLS QDKLEYEWFE FTLPEGNFSE TMTIDLMNNA ILENYLQVGR QNGVLESDIG VKFDSRNFKL GWDPVTKLVM PGVYTYEAFH PDVVLLPGCG VDFTESRLSN LLGIRKKQPF QEGFRIMYED LEGGNIPALL DVPKYLESKK KVEDETKNAA AATADTTTRG DTFATPAQET AADKKVEVLP IEKDESGRSY NLIQGTHDTL YRSWYLSYTY GDPEKGVQSW TLLTTPDVTC GAEQVYWSLP DLMQDPVTFR STQQVSNYPV VGAELMPFRA KSFYNDLAVY SQLIRSYTSL THVFNRFPDN QILCRPPAPT ITTVSENVPA LTDHGTLPLR SSIRGVQRVT VTDARRRTCP YVYKALGIVA PRVLSSRTF hAd11 (UniProt Acc. No. D2DM93); SEQ ID NO: 7: MRRVVLGGAV VYPEGPPPSY ESVMQQQATA VMQSPLEAPF VPPRYLAPTE GRNSIRYSEL APQYDTTRLY LVDNKSADIA SLNYQNDHSN FLTTVVQNND FTPTEASTQT INFDERSRWG GQLKTIMHTN MPNVNEYMFS NNFKARVMVS RKPPEGAAVG DTYDHKQDIL EYEWFEFTLP EGNFSVTMTI DLMNNAIIDN YLKVGRQNGV LESDIGVKFD TRNFKLGWDP ETKLIMPGVY TYEAFHPDIV LLPGCGVDFT ESRLSNLLGI RKKQPFQEGF KILYEDLEGG NIPALLDVDA Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys YENSKKEQKA KIEAAAEAKA NIVASDSTRV ANAGEVRGDN FAPTPVPTAE SLLADVSGGT DVKLTIQPVE KDSKNRSYNV LEDKINTAYR SWYLSYNYGD PEKGVRSWTL LTTSDVTCGA EQVYWSLPDM MQDPVTFRST RQVSNYPVVG AELMPVFSKS FYNEQAVYSQ QLRQSTSLTH VFNRFPENQI LIRPPAPTIT TVSENVPALT DHGTLPLRSS IRGVQRVTVT DARRRTCPYV YKALGIVAPR VLSSRTF hAd12 (UniProt Acc. No. P36716); SEQ ID NO: 8: MRRAVELQTV AFPETPPPSY ETVMAAAPPY VPPRYLGPTE GRNSIRYSEL SPLYDTTRVY LVDNKSSDIA SLNYQNDHSN FLTTVVQNND YSPIEAGTQT INFDERSRWG GDLKTILHTN MPNVNDFMFT TKFKARVMVA RKTNNEGQTI LEYEWAEFVL PEGNYSETMT IDLMNNAIIE HYLRVGRQHG VLESDIGVKF DTRNFRLGWD PETQLVTPGV YTNEAFHPDI VLLPGCGVDF TESRLSNILG IRKRQPFQEG FVIMYEHLEG GNIPALLDVK KYENSLQDQN TVRGDNFIAL NKAARIEPVE TDPKGRSYNL LPDKKNTKYR SWYLAYNYGD PEKGVRSWTL LTTPDVTGGS EQVYWSLPDM MQDPVTFRSS RQVSNYPVVA AELLPVHAKS FYNEQAVYSQ LIRQSTALTR VFNRFPENQI LVRPPAATIT TVSENVPALT DHGTLPLRSS ISGVQRVTIT DARRRTCPYV YKALGIVSPR VLSSRTF hAd15 (UniProt Acc. No. E1CIJ8); SEQ ID NO: 9: MRRAVVSSSP PPSYESVMAQ ATLEVPFVPP RYMAPTEGRN SIRYSELAPQ YDTTRVYLVD NKSADIASLN YQNDHSNFLT TVVQNNDFTP AEASTQTINF DERSRWGGDL KTILHTNMPN VNEYMFTSKF KARVMVARKH PENVAKEDLS QDILEYKWFE FTLPEGNFSE TMTIDLMNNA ILENYLQVGR QNGVLESDIG VKFDSRNFKL GWDPVTKLVM PGVYTYEAFH PDVVLLPGCG VDFTESRLSN LLGIRKKQPF QEGFRIMYED LEGGNIPALL DTKKYLDSKK ELEDAAKEAA KQQGDGAVTR GDTHLTVAQE KAAQKELVIV PIEKDESNRS YNLIKDTHDT LYRSWYLSYT YGDPEKGVQS WTLLTTPDVT CGAEQVYWSL PDLMQDPVTF RSTQQVSNYP VVGAELMPFR AKSFYNDLAV YSQLIRSYTS LTHVFNRFPD NQILCRPPAP TITTVSENVP ALTDHGTLPL RSSIRGVQRV TVTDARRRTC PYVYKALGIV APRVLSSRTF hAd17 (UniProt Acc. No. F1DT65); SEQ ID NO: 10: MRRAVVSSSP PPSYESVMAQ ATLEVPFVPP RYMAPTEGRN SIRYSELAPL YDTTRVYLVD NKSADIASLN YQNDHSNFLT TVVQNNDFTP AEASTQTINF DERSRWGGDL KTILHTNMPN VNEYMFTSKF KARVMVARKH PQGVEATDLS Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys KDILEYEWFE FTLPEGNFSE TMTIDLMNNA ILENYLQVGR QNGVLESDIG VKFDSRNFKL GWDPVTKLVM PGVYTYEAFH PDVVLLPGCG VDFTESRLSN LLGIRKKQPF QEGFRIMYED LEGGNIPALL DVPKYLESKK KLEEALENAA KANGPARGDS SVSREVEKAA EKELVIEPIK QDDSKRSYNL IEGTMDTLYR SWYLSYTYGD PEKGVQSWTL LTTPDVTCGA EQVYWSLPDL MQDPVTFRST QQVSNYPVVG AELMPFRAKS FYNDLAVYSQ LIRSYTSLTH VFNRFPDNQI LCRPPAPTIT TVSENVPALT DHGTLPLRSS IRGVQRVTVT DARRRTCPYV YKALGIVAPR VLSSRTF hAd25 (UniProt Acc. No. M0QUK0); SEQ ID NO: 11: MRRAVVSSSP PPSYESVMAQ ATLEVPFVPP RYMAPTEGRN SIRYSELAPQ YDTTRVYLVD NKSADIASLN YQNDHSNFLT TVVQNNDFTP AEASTQTINF DERSRWGGDL KTILHTNMPN VNEYMFTSKF KARVMVARKH PENVDKTDLS QDKLEYEWFE FTLPEGNFSE TMTIDLMNNA ILENYLQVGR QNGVLESDIG VKFDSRNFKL GWDPVTKLVM PGVYTYEAFH PDVVLLPGCG VDFTESRLSN LLGIRKKQPF QEGFRIMYED LEGGNIPALL DTKKYLDSKK ELEDAAKEAA KQQGDGAVTR GDTHLTVAQE KAAEKELVIV PIEKDESNRS YNLIKDTHDT MYRSWYLSYT YGDPEKGVQS WTLLTTPDVT CGAEQVYWSL PDLMQDPVTF RSTQQVSNYP VVGAELMPFR AKSFYNDLAV YSQLIRSYTS LTHVFNRFPD NQILCRPPAP TITTVSENVP ALTDHGTLPL RSSIRGVQRV TVTDARRRTC PYVYKALGIV APRVLSSRTF hAd35 (UniProt Acc. No. Q7T941); SEQ ID NO: 12: MRRVVLGGAV VYPEGPPPSY ESVMQQQQAT AVMQSPLEAP FVPPRYLAPT EGRNSIRYSE LAPQYDTTRL YLVDNKSADI ASLNYQNDHS NFLTTVVQNN DFTPTEASTQ TINFDERSRW GGQLKTIMHT NMPNVNEYMF SNKFKARVMV SRKPPDGAAV GDTYDHKQDI LEYEWFEFTL PEGNFSVTMT IDLMNNAIID NYLKVGRQNG VLESDIGVKF DTRNFKLGWD PETKLIMPGV YTYEAFHPDI VLLPGCGVDF TESRLSNLLG IRKKQPFQEG FKILYEDLEG GNIPALLDVD AYENSKKEQK AKIEAATAAA EAKANIVASD STRVANAGEV RGDNFAPTPV PTAESLLADV SEGTDVKLTI QPVEKDSKNR SYNVLEDKIN TAYRSWYLSY NYGDPEKGVR SWTLLTTSDV TCGAEQVYWS LPDMMKDPVT FRSTRQVSNY Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys PVVGAELMPV FSKSFYNEQA VYSQQLRQST SLTHVFNRFP ENQILIRPPA PTITTVSENV PALTDHGTLP LRSSIRGVQR VTVTDARRRT CPYVYKALGI VAPRVLSSRT F hAd37 (UniProt Acc. No. Q912J1); SEQ ID NO: 13 MRRAVVSSSP PPSYESVMAQ ATLEVPFVPP RYMAPTEGRN SIRYSELAPL YDTTRVYLVD NKSADIASLN YQNDHSNFLT TVVQNNDFTP AEASTQTINF DERSRWGGDL KTILHTNMPN VNEYMFTSKF KARVMVARKK AEGADANDRS KDILEYQWFE FTLPEGNFSE TMTIDLMNNA ILENYLQVGR QNGVLESDIG VKFDSRNFKL GWDPVTKLVM PGVYTYEAFH PDVVLLPGCG VDFTESRLSN LLGIRKKQPF QEGFRIMYED LVGGNIPALL NVKEYLKDKE EAGKADANTI KAQNDAVPRG DNYASAAEAK AAGKEIELKA ILKDDSDRSY NVIEGTTDTL YRSWYLSYTY GDPEKGVQSW TLLTTPDVTC GAEQVYWSLP DLMQDPVTFR STQQVSNYPV VGAELMPFRA KSFYNDLAVY SQLIRSYTSL THVFNRFPDN QILCRPPAPT ITTVSENVPA LTDHGTLPLR SSIRGVQRVT VTDARRRTCP YVYKALGIVA PRVLSSRTF hAd41 (UniProt Acc. No. F8WQN4); SEQ ID NO: 14: MRRAVGVPPV MAYAEGPPPS YESVMGSADS PATLEALYVP PRYLGPTEGR NSIRYSELAP LYDTTRVYLV DNKSADIASL NYQNDHSNFQ TTVVQNNDFT PAEAGTQTIN FDERSRWGAD LKTILRTNMP NINEFMSTNK FKARLMVEKK NKETGLPRYE WFEFTLPEGN YSETMTIDLM NNAIVDNYLE VGRQNGVLES DIGVKFDTRN FRLGWDPVTK LVMPGVYTNE AFHPDIVLLP GCGVDFTQSR LSNLLGIRKR LPFQEGFQIM YEDLEGGNIP ALLDVTKYEA SIQKAKEEGK EIGDDTFATR PQDLVIEPVA KDSKNRSYNL LPNDQNNTAY RSWFLAYNYG DPNKGVQSWT LLTTADVTCG SQQVYWSLPD MMQDPVTFRP STQVSNYPVV GVELLPVHAK SFYNEQAVYS QLIRQSTALT HVFNRFPENQ ILVRPPAPTI TTVSENVPAL TDHGTLPLRS SISGVQRVTI TDARRRTCPY VHKALGIVAP KVLSSRTF hAd49 (GenBank Acc. No. ABD52391.1); SEQ ID NO: 15: MRRAVVSSSP PPSYESVMAQ ATLEVPFVPP RYMAPTEGRN SIRYSELAPQ YDTTRVYLVD NKSADIASLN YQNDHSNFLT TVVQNNDFTP AEASTQTINF DERSRWGGDL KTILHTNMPN VNEYMFTSKF KARVMVSRKR PEGATDASQD Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys ILKYEWFEFL PEGNFSETMT IDLMNNAILE NYLQVGRQNG VLESDIGVKF DSRNFRLGWD PETKLVMPGV YTYEAFHPDV VLLPGCGVDF TESRLSNLLG IRKKQPFQEG FRIMYEDLEG GNIPALLDVE AYLKSKNDLE EATKNANRAA ANGGGETRGD TFLTTEQLRA AGKELVIKPI KEDASKRSYN VIGDTHDTLY RSWYLSYTYG DPEKGVQSWT LLTTPDVTCG AEQVYWSLPD LMQDPVTFRS TQQVSNYPVV GAELMPFRAK SFYNDLAVYS QLIRSYTSLT HVFNRFPDNQ ILCRPPAPTI TTVSENVPAL TDHGTLPLRS SIRGVQRVTV TDARRRTCPY VYKALGIVAP RVLSSRTF GorAd (E5L3Q9); SEQ ID NO: 16: MMRRAVLGGA VVYPEGPPPS YESVMQQQAA AVMQPSLEAP FVPPRYLAPT EGRNSIRYSE LAPQYDTTRL YLVDNKSADI ASLNYQNDHS NFLTTVVQNN DFTPTEASTQ TINFDERSRW GGQLKTIMHT NMPNVNEYMF SNKFKARVMV SREASKIDSE KNDRSKDTLK YEWFEFTLPE GNFSATMTID LMNNAIIDNY LAVGRQNGVL QSDIGVKFDT RNFRLGWDPV TKLVMPGVYT YEAFHPDIVL LPDCGVDFTE SRLSNLLGIR KRHPFQEGFK IMYEDLEGGN IPALLDVAEY EKSKKEIASS TTTTAVTTVA RNVADTSVEA VAVAVVDTIK AENDSAVRGD NFQSKNDMKA SEEVTVVPVS PPTVTETETK EPTIKPLEKD TKDRSYNVIS GTNDTAYRSW YLAYNYGDPE KGVRSWTLLT TSDVTCGAEQ VYWSLPDMMQ DPVTFRSTRQ VSNYPVVGAE LMPVFSKSFY NEQAVYSQQL RQTTSLTHIF DRFPENQILI RPPAPTITTV SENVPALTDH GTLPLRSSIR GVQRVTVTDA RRRTCPYVYK ALGIVAPRVL SSRTF Chimpanzee Adenovirus Penton Base Y25, ChAdY25 (UniProt Acc. No. G9G849); SEQ ID NO: 17: MMRRAYPEGP PPSYESVMQQ AMAAAAAMQP PLEAPYVPPR YLAPTEGRNS IRYSELAPLY DTTRLYLVDN KSADIASLNY QNDHSNFLTT VVQNNDFTPT EASTQTINFD ERSRWGGQLK TIMHTNMPNV NEFMYSNKFK ARVMVSRKTP NGVTVTDGSQ DILEYEWVEF ELPEGNFSVT MTIDLMNNAI IDNYLAVGRQ NGVLESDIGV KFDTRNFRLG WDPVTELVMP GVYTNEAFHP DIVLLPGCGV DFTESRLSNL LGIRKRQPFQ EGFQIMYEDL EGGNIPALLD VDAYEKSKEE SAAAATAAVA TASTEVRGDN FASPAAVAAA EAAETESKIV IQPVEKDSKD RSYNVLPDKI NTAYRSWYLA YNYGDPEKGV RSWTLLTTSD VTCGVEQVYW Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys SLPDMMQDPV TFRSTRQVSN YPVVGAELLP VYSKSFFNEQ AVYSQQLRAF TSLTHVFNRF PENQILVRPP APTITTVSEN VPALTDHGTL PLRSSIRGVQ RVTVTDARRR TCPYVYKALG IVAPRVLSSR TF Simian Adenovirus Serotype 18 Penton Base, sAd18 (UniProt Acc. No. H8PFZ9); SEQ ID NO: 18: MRRAVGVPPV MAYAEGPPPS YETVMGAADS PATLEALYVP PRYLGPTEGR NSIRYSELAP LYDTTRVYLV DNKSADIASL NYQNDHSNFL TTVVQNNDFT PVEAGTQTIN FDERSRWGGD LKTILRTNMP NINEFMSTNK FRARLMVEKV NKETNAPRYE WFEFTLPEGN YSETMTIDLM NNAIVDNYLE VGRQNGVLES DIGVKFDTRN FRLGWDPVTK LVMPGVYTNE AFHPDIVLLP GCGVDFTQSR LSNLLGIRKR MPFQAGFQIM YEDLEGGNIP ALLDVAKYEA SIQKAREQGQ EIRGDNFTVI PRDVEIVPVE KDSKDRSYNL LPGDQTNTAY RSWFLAYNYG DPEKGVRSWT LLTTTDVTCG SQQVYWSLPD MMQDPVTFRP SSQVSNYPVV GVELLPVHAK SFYNEQAVYS QLIRQSTALT HVFNRFPENQ ILVRPPAPTI TTVSENVPAL TDHGTLPLRS SISGVQRVTI TDARRRTCPY VHKALGIVAP KVLSSRTF sAd20 (UniProt Acc. No. F6KSU4); SEQ ID NO: 19: MRRAVAIPSA AVALGPPPSY ESVMASANLQ APLENPYVPP RYLEPTGGRN SIRYSELTPL YDTTRLYLVD NKSADIATLN YQNDHSNFLT SVVQNSDYTP AEASTQTINL DDRSRWGGDL KTILHTNMPN VNEFMFTNSF RAKLMVAHET NKDPVYKWVE LTLPEGNFSE TMTIDLMNNA IVDHYLAVGR QNGVKESEIG VKFDTRNFRL GWDPQTELVM PGVYTNEAFH PDVVLLPGCG VDFTYSRLSN LLGIRKRMPF QEGFQIMYED LVGGNIPALL DVPAYEASIT TVAAKEVRGD NFEAAAAAAA TGAQPQAAPV VRPVTQDSKG RSYNIITGTN NTAYRSWYLA YNYGDPEKGV RSWTLLTTPD VTCGSEQVYW SMPDMYVDPV TFRSSQQVSS YPVVGAELLP IHSKSFYNEQ AVYSQLIRQQ TALTHVFNRF PENQILVRPP APTITTVSEN VPALTDHGTL PLQNSIRGVQ RVTITDARRR TCPYVYKALG IVAPRVLSSR TF sAd49 (UniProt Acc. No. F2WTK5); SEQ ID NO: 20: MRRAVPAAAI PATVAYADPP PSYESVMAGV PATLEAPYVP PRYLGPTEGR Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys NSIRYSELAP LYDTTRVYLV DNKSADIASL NYQNDHSNFL TTVVQNNDFT PVEAGTQTIN FDERSRWGGQ LKTILHTNMP NVNEFMFTNS FRAKVMVSRK QNEEGQTELE YEWVEFVLPE GNYSETMTLD LMNNAIVDHY LLVGRQNGVL ESDIGVKFDT RNFRLGWDPV TKLVMPGVYT NEAFHPDVVL LPGCGVDFTQ SRLSNLLGIR KRQPFQEGFR IMYEDLEGGN IPALLNVKAY EDSIAAAMRK HNLPLRGDVF AVQPQEIVIQ PVEKDGKERS YNLLPDDKNN TAYRSWYLAY NYGDPLKGVR SWTLLTTPDV TCGSEQVYWS LPDLMQDPVT FRPSSQVSNY PVVGAELLPL QAKSFYNEQA VYSQLIRQST ALTHVFNRFP ENQILVRPPA ATITTVSENV PALTDHGTLP LRSSISGVQR VTITDARRRT CPYVYKALGI VAPRVLSSRT F Rhesus Adenovirus Serotype 51 Penton Base, rhAd51 (UniProt Acc. No. A0A0A1EWW1); SEQ ID NO: 21: MRRAVRVTPA AYEGPPPSYE SVMGSANVPA TLEAPYVPPR YLGPTEGRNS IRYSELAPLY DTTKVYLVDN KSADIASLNY QNDHSNFLTT VVQNNDFTPT EAGTQTINFD ERSRWGGQLK TILHTNMPNI NEFMSTNKFR AKLMVEKSNA ETRQPRYEWF EFTIPEGNYS ETMTIDLMNN AIVDNYLQVG RQNGVLESDI GVKFDTRNFR LGWDPVTKLV MPGVYTNEAF HPDIVLLPGC GVDFTQSRLS NLLGIRKRRP FQEGFQIMYE DLEGGNIPAL LDVSKYEASI QRAKAEGREI RGDTFAVAPQ DLEIVPLTKD SKDRSYNIIN NTTDTLYRSW FLAYNYGDPE KGVRSWTILT TTDVTCGSQQ VYWSLPDMMQ DPVTFRPSTQ VSNFPVVGTE LLPVHAKSFY NEQAVYSQLI RQSTALTHVF NRFPENQILV RPPAPTITTV SENVPALTDH GTLPLRSSIS GVQRVTITDA RRRTCPYVYK ALGVVAPKVL SSRTF rhAd52 (UniProt Acc. No. A0A0A1EWX7); SEQ ID NO: 22: MRRAVRVTPA AYEGPPPSYE SVMGSANVPA TLEAPYVPPR YLGPTEGRNS IRYSELAPLY DTTKVYLVDN KSADIASLNY QNDHSNFLTT VVQNNDFTPT EAGTQTINFD ERSRWGGQLK TILHTNMPNI NEFMSTNKFR ARLMVKKVEN QPPEYEWFEF TIPEGNYSET MTIDLMNNAI VDNYLQVGRQ NGVLESDIGV KFDTRNFRLG WDPVTKLVMP GVYTNEAFHP DIVLLPGCGV DFTQSRLSNL LGIRKRRPFQ EGFQIMYEDL EGGNIPALLD VTKYEQSVQR AKAEGREIRG DTFAVSPQDL VIEPLEHDSK NRSYNLLPNK TDTAYRSWFL AYNYGDPEKG Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys VRSWTILTTT DVTCGSQQVY WSLPDMMQDP VTFRPSTQVS NFPVVGTELL PVHAKSFYNE QAVYSQLIRQ STALTHVFNR FPENQILVRP PAPTITTVSE NVPALTDHGT LPLRSSISGV QRVTITDARR RTCPYVYKAL GVVAPKVLSS RTF rhAd53 (UniProt Acc. No. A0A0A1EWZ7); SEQ ID NO: NO 23: MRRAVRVTPA VYAEGPPPSY ESVMGSANVP ATLEAPYVPP RYLGPTEGRN SIRYSELAPL YDTTKVYLVD NKSADIASLN YQNDHSNFLT TVVQNNDFTP TEAGTQTINF DERSRWGGQL KTILHTNMPN INEFMSTNKF RARLMVEKTS GQPPKYEWFE FTIPEGNYSE TMTIDLMNNA IVDNYLQVGR QNGVLESDIG VKFDTRNFRL GWDPVTKLVM PGVYTNEAFH PDIVLLPGCG VDFTQSRLSN LLGIRKRRPF QEGFQIMYED LEGGNIPGLL DVPAYEQSLQ QAQEEGRVTR GDTFATAPNE VVIKPLLKDS KDRSYNIITD TTDTLYRSWF LAYNYGDPEN GVRSWTILTT TDVTCGSQQV YWSLPDMMQD PVTFRPSTQV SNFPVVGTEL LPVHAKSFYN EQAVYSQLIR QSTALTHVFN RFPENQILVR PPAPTITTVS ENVPALTDHG TLPLRSSISG VQRVTITDAR RRTCPYVYKA LGVVAPKVLS SRTF Highly preferred adenovirus penton base polypeptides are or are derived from, respectivelly, penton base polypetides of hAd3, hAd4, hAd7, hAd9, hAd11 and hAd15. In further preferred embodiments the adenovirus penton base polypeptide(s) is/are or is/are derived from, respectively, ChAdY25. In other embodiments of the invention, the adenovirus penton base protomer polypeptides are derived from chimeric adenovirus penton base protomers comprising a jelly fold roll domain of a first adenovirus type and a head domain of a second adenovirus type wherein the first and second adenovirus types are different, as disclosed in WO 2021/156489 A1. Preferably, the first and the second adenovirus types are selected from the adenovirus types, or mutants thereof, as outlined herein. The adenovirus penton base protomer polypeptides for use in the invention may also be modified at their N and/or C termini or may be modified in one or more of the first RGD loop, the second RGD loops and the V loop (also known as “VL loop”), preferably as disclosed in WO 2017/167988 A1. With respect to the definition of the first RGD loop, the second RGD loop and the V loop it is referred to the disclosure of WO 2017/167988 A1, page 32, line 8, to page 33, line 28. Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys One preferred kind of mutants for use in the invention concerns the introduction of one or more coupling residues as outlined above into a wildtype adenovirus penton base protomer polypeptide. As described in WO 2017/167988 A1 the N-terminal domain of the adenovirus penton base protomer polypeptide is involved in the interaction between the penton base protomer polypeptides within a pentamer (i.e. the adenovirus penton) and also in the interaction among pentons forming a VLP. The insertion of coupling residues into this region allows the formation of covalent bonds between two or more penton base protomers within the same or separate pentons. The formation of such covalent bonds stabilizes the penton as well as the assembled VLP. The N-terminal domain is highly conserved among different adenovirus species. It is, therefore possible to further delineate the N-terminal and C-terminal end of this domain within the penton base protomer. Thus, it is preferred that one or more the coupling residues are comprized in the N-terminal domain. The coupling residue may replace an existing amino acid or may be inserted in addition to the amino acids forming the N-terminal domain. It is preferred that the one or more coupling residue replace a residue within the N- terminal domain. The N-terminus of the N-terminal domain within the penton base protomer polypeptide is preferably defined as follows: X-G-R-N-S-I-R (SEQ ID NO: 29) and the C-terminus of the N-terminal domain within the penton base protomer is preferably defined as follows: D-X-R-S-R-G (SEQ ID NO: 30), wherein X3 is selected from the group consisting of G and E, preferably E, and X4 is selected from the group consisting of D and E. In such embodiments of the invention one or more coupling residues may be comprized within the amino acid sequence of the penton base protomer polypeptides comprized in the polypeptide assembly of the present invention delimited by above N- and C-terminal region, respectively. It will be understood by the skilled person that it is also possible in this embodiment to replace one or more amino acid residues within SEQ ID NO: 29 or 30. The coupling residue may be positioned anywhere within the N-terminal domain as long as same does not interfere with the formation of the at least five adenovirus penton base protomer polypeptides in the polypeptide assembly according to the invention, and more preferably, as long as the introduction of the coupling residue does not interfere with the formation of a VLP, i.e.12 pentamers of component (ii) or the assembly according to the invention. Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys Preferably, there has to be a pair of coupling residues, preferably mutations to cysteines to enable disulfide bond formation. The resulting stabilized VLP contains up to 120 disulfide bonds and is hyperstable at 37°C and even at 42°C, at least for several months such for 2, 3, 4, 5, 6 or more months. In a preferred embodiment, the coupling residues are located at amino acid position 51 and 54 with reference to SEQ ID NO: 1, i.e. a preferred penton base protomer polypeptide amino acid sequence based on hAd3 or at analogous positions of a penton base protomer polypeptide of another adenovirus, or at amino acid position 54 and 114 with reference to SEQ ID NO: 1 or at analogous positions of a penton base protomer polypeptide of another adenovirus. It has been further discovered that a coupling residue at amino acid position 53 (with reference to SEQ ID NO: 1) can form a covalent bond with a coupling residue at amino acid position 526 (with reference to SEQ ID NO: 1) or at analogous positions of a penton base protomer polypeptide of another adenovirus. The latter residue is outside the N-terminal domain. Thus, if a coupling residue is inserted at position 53 it is preferred that a second coupling residue is positioned at amino acid 526 with reference to SEQ ID NO: 1 or at analogous positions of a penton base protomer of another adenovirus. With reference to Fig. 6 of WO 2017/167988 A1 and by including further penton base protomer polypeptide sequence in the alignment the skilled person can readily determine those residues in the respective penton base protomer polypeptide that occupies an analogous position as amino acids.51, 53, 54, 114 and 526 of SEQ ID NO: 1. It is preferred in this embodiment of the polypeptide assembly of the present invention that at least one, preferably all of the adenovirus penton base protomer polypeptide(s) of component (i) comprise(s) the following sequences: P-T-X-Xc-R-N-Xc-I-R (SEQ ID NO: 31); P-T-X-G-R-Xc-S-I-R (SEQ ID NO: 32) andT-Q-T-I-N-X-Xc-X (SEQ ID NO: 33) or P-T-X-G-R-N-Xc-I-R (SEQ ID NO: 34) and T-C-P-Xc-V-X -K-A-L-G (SEQ ID NO: 35) wherein X ₃ is selected from the group consisting of G and E, preferably E Xc in each case is a coupling residue, preferably selected from the group consisting of C; D, E, and K, most preferably C; Χ ₅ is selected from the group consisting of F, I, and L, preferably F and L, most preferably F, Χ ₆ is selected from the group consisting of D and E, preferably E; and X ₇ is selected from the group consisting of H and Y, preferably Y. Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys Particularly preferred stabilized adenovirus penton base protomer polypeptides for use in the invention comprise or consist of, respectively the amino acid sequences according to SEQ ID NO: 36 to 38 (presented from N- to C-terminal in the three letter code of amino acids). SEQ ID NO: 36 (coupling residues at positions 51 and 54): Met Arg Arg Arg Ala Val Leu Gly Gly Ala Val Val Tyr Pro Glu Gly Pro Pro Pro Ser Tyr Glu Ser Val Met Gln Gln Gln Ala Ala Met Ile Gln Pro Pro Leu Glu Ala Pro Phe Val Pro Pro Arg Tyr Leu Ala Pro Thr Glu Cys Arg Asn Cys Ile Arg Tyr Ser Glu Leu Ser Pro Leu Tyr Asp Thr Thr Lys Leu Tyr Leu Val Asp Asn Lys Ser Ala Asp Ile Ala Ser Leu Asn Tyr Gln Asn Asp His Ser Asn Phe Leu Thr Thr Val Val Gln Asn Asn Asp Phe Thr Pro Thr Glu Ala Ser Thr Gln Thr Ile Asn Phe Asp Glu Arg Ser Arg Trp Gly Gly Gln Leu Lys Thr Ile Met His Ala Arg Val Met Val Ser Arg Lys Ala Pro Glu Gly Glu Phe Val Thr Val Asn Asp Gly Pro Val Asn Asp Thr Tyr Asp His Lys Glu Asp Ile Leu Lys Tyr Glu Trp Phe Glu Phe Ile Leu Pro Glu Gly Asn Phe Ser Ala Thr Met Thr Ile Asp Leu Met Asn Asn Ala Ile Ile Asp Asn Tyr Leu Glu Ile Gly Arg Gln Asn Gly Val Leu Glu Ser Asp Ile Gly Val Lys Phe Asp Thr Arg Asn Phe Arg Leu Gly Trp Asp Pro Glu Thr Lys Leu Ile Met Pro Gly Val Tyr Thr Tyr Glu Ala Phe His Pro Asp Ile Val Leu Leu Pro Gly Cys Gly Val Asp Phe Thr Glu Ser Arg Leu Ser Asn Leu Leu Gly Ile Arg Lys Arg His Pro Phe Gln Glu Gly Phe Lys Ile Met Tyr Glu Asp Leu Glu Gly Gly Asn Ile Pro Ala Leu Leu Asp Val Thr Ala Tyr Glu Glu Ser Lys Lys Asp Thr Thr Thr Ala Arg Glu Thr Thr Thr Leu Ala Val Ala Glu Glu Thr Ser Glu Asp Val Asp Asp Asp Ile Thr Arg Gly Asp Thr Tyr Ile Thr Glu Leu Glu Lys Gln Lys Arg Glu Ala Ala Ala Ala Glu Val Ser Arg Lys Lys Glu Leu Lys Ile Gln Pro Leu Glu Lys Asp Ser Lys Ser Arg Ser Tyr Asn Val Leu Glu Asp Lys Ile Asn Thr Ala Tyr Arg Ser Trp Tyr Leu Ser Tyr Asn Tyr Gly Asn Pro Glu Lys Gly Ile Arg Ser Trp Thr Leu Leu Thr Thr Ser Met Gln Asp Pro Val Thr Phe Arg Ser Thr Arg Gln Val Asn Asn Tyr Pro Val Val Gly Ala Glu Leu Met Pro Val Phe Ser Lys Ser Phe Tyr Asn Glu Gln Ala Val Tyr Ser Gln Gln Leu Arg Gln Ala Thr Ser Leu Thr His Val Phe Asn Arg Phe Pro Glu Asn Gln Ile Leu Ile Arg Pro Pro Ala Pro Thr Ile Thr Thr Val Ser Glu Asn Val Pro Ala Leu Thr Asp His Gly Thr Leu Pro Leu Arg Ser Ser Ile Arg Gly Val Gln Arg Val Thr Val Thr Asp Ala Arg Arg Arg Thr Cys Pro Tyr Val Tyr Lys Ala Leu Gly Ile Val Ala Pro Arg Val Leu Ser Ser Arg Thr Phe Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys SEQ ID NO: 37 (coupling residues at positions 54 and 114): Met Arg Arg Arg Ala Val Leu Gly Gly Ala Val Val Tyr Pro Glu Gly Pro Pro Pro Ser Tyr Glu Ser Val Met Gln Gln Gln Ala Ala Met Ile Gln Pro Pro Leu Glu Ala Pro Phe Val Pro Pro Arg Tyr Leu Ala Pro Thr Glu Gly Arg Asn Cys Ile Arg Tyr Ser Glu Leu Ser Pro Leu Tyr Asp Thr Thr Lys Leu Tyr Leu Val Asp Asn Lys Ser Ala Asp Ile Ala Ser Leu Asn Tyr Gln Asn Asp His Ser Asn Phe Leu Thr Thr Val Val Ile Asn Phe Cys Glu Arg Ser Arg Trp Gly Gly Gln Leu Lys Thr Ile Met His Thr Asn Met Pro Asn Val Asn Glu Tyr Met Phe Ser Asn Lys Phe Lys Ala Arg Val Met Val Ser Arg Lys Ala Pro Glu Gly Glu Phe Val Thr Val Asn Asp Gly Pro Val Asn Asp Thr Tyr Asp His Lys Glu Asp Ile Leu Lys Tyr Glu Trp Phe Glu Phe Ile Leu Pro Glu Gly Asn Phe Ser Ala Thr Met Thr Ile Asp Leu Met Asn Asn Ala Ile Ile Asp Asn Tyr Leu Glu Ile Gly Arg Gln Asn Gly Val Leu Glu Ser Asp Ile Gly Val Lys Phe Asp Thr Arg Asn Phe Arg Leu Gly Trp Asp Pro Glu Thr Lys Leu Ile Met Pro Gly Val Tyr Thr Tyr Glu Ala Phe His Pro Asp Ile Val Leu Leu Pro Gly Cys Gly Val Asp Phe Thr Glu Ser Arg Leu Ser Asn Leu Leu Gly Ile Arg Lys Arg His Pro Phe Gln Glu Gly Phe Lys Ile Met Tyr Glu Asp Leu Glu Gly Gly Asn Ile Pro Ala Leu Leu Asp Val Thr Ala Tyr Glu Glu Ser Lys Lys Asp Thr Thr Thr Ala Arg Glu Thr Thr Thr Leu Ala Val Ala Glu Glu Thr Ser Glu Asp Val Asp Asp Asp Ile Thr Arg Gly Asp Thr Tyr Ile Thr Glu Leu Glu Lys Gln Lys Arg Glu Ala Ala Ala Ala Glu Val Ser Arg Lys Lys Glu Leu Lys Ile Gln Pro Leu Glu Lys Asp Ser Lys Ser Arg Ser Tyr Asn Val Leu Glu Asp Lys Ile Asn Thr Ala Tyr Arg Ser Trp Tyr Leu Ser Tyr Asn Tyr Gly Asn Pro Glu Lys Gly Ile Arg Ser Trp Thr Leu Leu Thr Thr Ser Asp Val Thr Cys Gly Ala Glu Gln Val Tyr Trp Ser Leu Pro Asp Met Met Gln Asp Pro Val Thr Phe Arg Ser Thr Arg Gln Val Asn Asn Tyr Pro Val Val Gly Ala Glu Leu Met Pro Val Phe Ser Lys Ser Phe Tyr Asn Glu Gln Ala Val Tyr Ser Gln Gln Leu Arg Gln Ala Thr Ser Leu Thr His Val Phe Asn Arg Phe Pro Glu Asn Gln Ile Leu Ile Arg Pro Pro Ala Pro Thr Ile Thr Thr Val Ser Glu Asn Val Pro Ala Leu Thr Asp His Gly Thr Leu Pro Leu Arg Ser Ser Ile Arg Gly Val Gln Arg Val Thr Val Thr Asp Ala Arg Arg Arg Thr Cys Pro Tyr Val Tyr Lys Ala Leu Gly Ile Val Ala Pro Arg Val Leu Ser Ser Arg Thr Phe SEQ ID NO: 38 (coupling residues at positions 51 and 541) Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys Met Arg Arg Arg Ala Val Leu Gly Gly Ala Val Val Tyr Pro Glu Gly Pro Pro Pro Ser Tyr Glu Ser Val Met Gln Gln Gln Ala Ala Met Ile Gln Pro Pro Leu Glu Ala Pro Phe Val Pro Pro Arg Tyr Leu Ala Pro Thr Glu Gly Arg Cys Ser Ile Arg Tyr Ser Glu Leu Ser Pro Leu Tyr Asp Thr Thr Lys Leu Tyr Leu Val Asp Asn Lys Ser Ala Asp Ile Ala Ser Leu Asn Tyr Gln Asn Asp His Ser Asn Phe Leu Thr Thr Val Val Gln Asn Asn Asp Phe Thr Pro Thr Glu Ala Ser Thr Gln Thr Ile Asn Phe Asp Glu Arg Ser Arg Trp Gly Gly Gln Leu Lys Thr Ile Met His Thr Asn Met Pro Asn Val Asn Glu Tyr Met Phe Ser Asn Lys Phe Lys Ala Arg Val Met Val Ser Arg Lys Ala Pro Glu Gly Glu Phe Val Thr al Asn Asp Gly Pro Val Asn Asp Thr Tyr Asp His Lys Glu Asp Ile Leu Lys Tyr Glu Trp Phe Glu Phe Ile Leu Pro Glu Gly Asn Phe Ser Ala Thr Met Thr Ile Asp Leu Met Asn Asn Ala Ile Ile Asp Asn Tyr Leu Glu Ile Gly Arg Gln Asn Gly Val Leu Glu Ser Asp Ile Gly Val Lys Phe Asp Thr Arg Asn Phe Arg Leu Gly Trp Asp Pro Glu Thr Lys Leu Ile Met Pro Gly Val Tyr Thr Tyr Glu Ala Phe His Pro Asp Ile Val Leu Leu Pro Gly Cys Gly Val Asp Phe Thr Glu Ser Arg Leu Ser Asn Leu Leu Gly Ile Arg Lys Arg His Pro Phe Gln Glu Gly Phe Lys Ile Met Tyr Glu Asp Leu Glu Gly Gly Asn Ile Pro Ala Leu Leu Asp Val Thr Ala Tyr Glu Glu Ser Lys Lys Asp Thr Thr Thr Ala Arg Glu Thr Thr Thr Leu Ala Val Ala Glu Glu Thr Ser Glu Asp Val Asp Asp Asp Ile Thr Arg Gly Asp Thr Tyr Ile Thr Glu Leu Glu Lys Gln Lys Arg Glu Ala Ala Ala Ala Glu Val Ser Arg Lys Lys Glu Leu Lys Ile Gln Pro Leu Glu Lys Asp Ser Lys Ser Arg Ser Tyr Asn Val Leu Glu Asp Lys Ile Asn Thr Ala Tyr Arg Ser Trp Tyr Leu Ser Tyr Asn Tyr Gly Asn Pro Glu Lys Gly Ile Arg Ser Trp Thr Leu Leu Thr Thr Ser Asp Val Thr Cys Gly Ala Glu Gln Val Tyr Trp Ser Leu Pro Asp Met Met Gln Asp Pro Val Thr Phe Arg Ser Thr Arg Gln Val Asn Asn Tyr Pro Val Val Gly Ala Glu Leu Met Pro Val Phe Ser Lys Ser Phe Tyr Asn Glu Gln Ala Val Tyr Ser Gln Gln Leu Arg Gln Ala Thr Ser Leu Thr His Val Phe Asn Arg Phe Pro Glu Asn Gln Ile Leu Ile Arg Pro Pro Ala Pro Thr Ile Thr Thr Val Ser Glu Asn Val Pro Ala Leu Thr Asp His Gly Thr Leu Pro Leu Arg Ser Ser Ile Arg Gly Val Gln Arg Val Thr Val Thr Asp Ala Arg Arg Arg Thr Cys Pro Cys Val Tyr Lys Ala Leu Gly Ile Val Ala Pro Arg Val Leu Ser Ser Arg Thr Phe The term "adenovirus fiber protein binding cleft" as used in the context of the present invention refers to a fold of a penton base protomer forming the interaction surface with the adenovirus fiber protein. As can be seen in Fig.6 of WO 2017/167988 A1 the binding cleft is Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys formed by several non- contiguous stretches of polypeptide sequence which are conserved among different adenoviruses. According to the invention, (sub-)component (1), namely the at least one adenovirus fiber protein N-terminal fragment specifically binding to an adenovirus fiber protein binding cleft of a penton base protomer (also referred to herein as STICKER; see also WO WO 2017/167988 A1), is typically a relatively small N-terminal fragment of an adenovirus fiber protein sufficient to specifically bind to (sub-)component (i) (at least one pentamer of adenovirus penton base protomer polypeptides) at the adenovirus fiber protein binding cleft. In general, the smaller the fiber fragment of (sub-)component (1) the bigger the moiety that can be attached to component (i). Furthermore, the reduction of the length of the adenoviral fiber fragment of component (1) reduces the likelihood that a new immune response is elicited against adenovirus fiber and/or that fiber bound to the pentameric component (i) and/or the VLPs according to the invention are cleared by preexisting anti-fiber antibodies. It is, thus preferred that the fiber fragment has a length of 50 contiguous amino acids or less of N-terminal fiber sequence. It is more preferred that the length of component (1) is 40 amino acids or less, 35 amino acids or less, 30 amino acids or less, 25 amino acids or less or 20 amino acids or less. Preferably, the minimal fiber amino acid sequence according to (sub- )component (1) of the polypeptide assembly of the invention required for specific binding to the binding cleft of the penton base protomer is F-N-P-V-Y-P-Y (SEQ ID: NO.24). This minimal sequence is preferably flanked by other adenovirus fiber e.g., derived from hAd3 or ChAdY25, amino acid sequences on both sides. According to the invention, this small fragment is preferably used for increasing the number of component (3a) and/or (3b) exposed on the surface of the VLP according to the invention. The presence of the STICKER tag (i.e. (sub-) component (1)) in component (ii) enables the binding of the cargo, namely (sub-) component (3a) and/or (sub-)component (3b) to the surface of component (i), and in turn to the surface of the VLP of the invention comprising 12 pentamers of component (i). This is preferably achieved by in vitro incubation of component (ii) with component (i), preferably in the form of 12 units of component (i), or by co-expression of both components (i) and (ii) in an eucaryotic expression system, preferably a baculovirus expression system. It is preferred that components (i), (2), (3a) and (3b) do not comprise any further fiber amino acid sequence contiguous with (sub-)component (1). More preferably, (sub-)component (1) of the polypeptide assembly of the invention does not comprise any other adenovirus proteins or polypeptides other than STICKER. Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys In preferred embodiments of the invention (sub-)component (1) of the polypeptide assembly comprises the sequence X-F-N-P-V-Y-P-X-X (SEQ ID NO: 25) wherein X ₀ is selected from the group consisting of S, D and T, preferably S or D, and is more preferably S; X ₁ is selected from and Y and F, and is preferably Y; and X ₂ is selected from the group consisting of E, D and G, is preferably E or D, and is more preferably E. Preferably, component (1) has a length of between 9 to 20 contiguous amino acids of an adenovirus fiber protein at least including the above-defined minimal fiber cleft binding sequence SEQ ID NO: 24, more preferably the fiber cleft binding sequence according to SEQ ID NO: 25. In certain preferred embodiments of the invention (sub-)component (1) comprises 2, 3, 4, 5, 6, 7, or 8 repeats of said N-terminal binding fragment of the fiber protein, particularly for increasing binding affinity to the adenovirus fiber binding cleft. As disclosed in WO 2017/167988 A1, 2 or 3, preferably consecutive repeats of the fiber protein fragment are suitable to mediate binding to the fiber binding cleft on component (i) with sub nanomolar affinities. Preferably, the multimers are arranged in a head-to-tail orientation. As mentioned above, component (ii) may be bound to component (i) via non-covalent or covalent interactions. In certain embodiments of the invention employing covalent binding of component (ii) to component (i), it is preferred that one or more coupling residues are comprised in the binding cleft of the penton base protomer polypeptide(s) of component (i), especially for facilitating the formation of covalent bonds between these one or more coupling residues in the adenovirus penton base protomer polypeptide(s) and coupling residues comprised in (sub-)component (1). In a preferred embodiment the at least one coupling residue is inserted into and/or positioned at the N- and/or C-terminus of the fiber protein fragment, preferably inserted into and/or positioned at the N- and/or C-terminus of SEQ ID NO: 25 or attached to an amino acid of (sub-)component (1). As has been set out above coupling residues have to form covalent bonds with corresponding coupling residues. Once two polypeptides interact it is preferred that the coupling residue of the one polypeptide is sterically close to the coupling residue in the other polypeptide. In a preferred embodiment of covalent binding of component (ii) to component (i), the coupling residue is positioned in Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys the adenovirus penton base protomer polypeptide at amino acid position 461 and/or 462 (with reference to the amino acid sequence of SEQ ID NO: 1) or at an analogous amino acid position of a penton base protomer polypeptide of another adenovirus. The analogous position in another adenovirus penton base protomer polypeptide can be determined by aligning the sequence according to SEQ ID NO: 1 with other adenoviral penton base protomer polypeptide amino acid sequences using a standard alignment tool known in the art such e.g., CLUSTAL. The skilled person can easily determine the amino acid that occupies an analogous position to amino acids 461 or 462 according to SEQ ID NO: 1 in another adenovirus penton base protomer polypeptide. In certain embodiments of the invention, it is preferred that at least one, preferably each of the adenovirus penton base protomer polypeptides of component (i) comprise(s) the sequence K-S-F-X-N-X X -A-V-Y (SEQ ID NO: 39) wherein X8 is selected from the group consisting of Y and F, preferably Y; Xc1 is selected from the group consisting of D, E and a coupling residue, preferably Cys; Xc2 is selected from the group consisting of L, Q and a coupling residue, preferably Cys; and wherein at least one, preferably both Xc1 and Xc2 are each a coupling residue, preferably Cys. If a coupling residue in the adenovirus penton base protomer polypeptides is positioned at either amino acid position 476 and/or 477 of SEQ ID NO: 1 or at an analogous amino acid position of an adenovirus penton base protomer polypeptide of another adenovirus, it is preferred that a corresponding coupling residue at the C- terminus of (sub-)component (1) is present. It is preferred that the coupling residue is located in the STICKER sequence of (sub-)component (1) as shown in the following sequence: X-F-N-P-V-Y-P-Y-X -(X )-Xc (SEQ ID NO: 40) wherein X9 is selected from the group consisting of S, D and T, preferably S or D, and is more preferably S; and X10 is selected from the group consisting of E, D and G, is preferably E or D, and is more preferably E; X ₁₁ is in each case independently any amino acid, preferably those naturally occurring in adenovirus fiber proteins at this or these positions; Xc is a coupling residue, preferably C, D, E, and K, most preferably C; and n is zero or an integer of 1 to 10, i.e.1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, preferably 2 to 4 or 5, more preferably 2. Thus, in preferred embodiments of the invention, (sub-)component (1) may comprise a STICKER sequence according to SEQ ID NO: 40. A particularly preferred amino acid sequence that may be comprised in (sub-)component (1) is Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys A-K-R-A-R-L-S-T-X-F-N-P-V-Y-P-Y-X -D-E-Xc (SEQ ID NO: 41) wherein X ₉ is selected from the group consisting of S, D and T, preferably S or D, and is more preferably S; X ₁₀ is selected from the group consisting of E, D and G, is preferably E or D, and is more preferably E; and Xc is a coupling residue, preferably C, D, E, and K, most preferably C. In a particularly preferred embodiment, the STICKER sequence of component (1) comprises the coupling residue Cys at position 20 and consists of the following amino acid sequence: A-K-R-A-R-L-S-T-S-F-N-P-V-Y-P-Y-E-D-E-C (SEQ ID NO: 42). In an alternative preferred embodiment, a coupling residue is positioned in the adenovirus penton base protomer polypeptides of component (i) at position 361 of the adenovirus penton base protomer polypeptide according to SEQ ID NO: 1 or an analogous position of a penton base protomer polypeptide of another adenovirus. In certain embodiments of the invention, the adenovirus penton base protomer polypeptides of component (i) preferably comprise the following sequence: Xc-X -R-S-Y-N (SEQ ID NO: 43) wherein Xc is a coupling residue, preferably selected from C, D, E, and K, and is most preferably C; and X12 is any amino acid, is preferably selected from the group consisting of D, E, G, K, N, or S, more preferably S or N. If the coupling residue is comprized at the position according to SEQ ID NO: 43, it is preferred that the (sub-)component (1) comprises a corresponding coupling residue as indicated in the following amino acid sequence: Xc -F-N-P-V-Y-P-Y-X (SEQ ID NO: 44) wherein X ₁₀ is selected from the group consisting of E, D and G, is preferably E or D, and is more preferably E; and Xc is a coupling residue, preferably selected from C, D, E, and K, and is most preferably C. Accordingly, (sub-)component (1) comprises in a preferred embodiment a STICKER sequence according to SEQ ID NO: 44. A particularly preferred embodiment of the above type that may be comprized in (sub-)component (1) is the sequence Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys A-K-R-A-R-L-S-T-Xc-F-N-P-V-Y-P-Y-X -D-E-S (SEQ ID NO: 45) wherein Xc is a coupling residue, preferably selected from C, D, E, and K, and is most preferably C; and X ₁₀ is selected from the group consisting of E, D and G, is preferably E or D, and is more preferably E. In a particularly preferred embodiment (sub-)component (1) comprises the coupling residue Cys at position 9 and consists of the following amino acid sequence: A-K-R-A-R-L-S-T-C-F-N-P-V-Y-P-Y-E-D-E-S (SEQ ID NO: 46). Preferably, the assembly of the invention comprises a dodecamer of (i.e.12 entities or copies, respectively, of) component (i). More preferably, the assembly of the invention including a dodecamer of component (i), and comprises 1 to 12, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12, multimers of component (ii), wherein the multimers (i.e. the degree of multimerization), correspond to the multimerization domains contained in the respective component(s) (ii), preferably being selected from dimers, trimers, tetramers and pentamers. A preferred assembly of the invention comprises or consists of 12 pentamers of component (i) and comprises at least one component (ii) bound to one of the 12 pentamers of component (i), more preferably the assembly comprises or consists of 12 components (ii) wherein each of the 12 compounds is bound to one pentamer of component (i). An assembly of the invention comprising a dodecamer of component (i) and 1 to 12 multimers of component (ii) is herein also denoted as a “Gigabody”. The dodecameric assembly of the invention, whether comprising bound component(s) (ii) or not (however, preferably comprising 1 to 12 multimers of compound (ii) is also denoted as a virus-like particle (VLP). Depending on the multiplicity of the multimer of component (ii) in the Gigabody, a huge multiplicity of presentation of the cargo (i.e. a drug and/or non-adenoviral peptide) present in component (ii). Thus, for example, in preferred embodiments according to which the Gigabody comprises 12 multimers of component (ii), the Gigabody can contain up to, preferably equal to, 36 non-adenoviral peptides and/or drugs, if component (ii) is a trimeric entity due to the presence of a trimerization domain contained therein. In other embodiments of the invention, the Gigabody carries up to, preferably equal to, 24 non-adenoviral peptides and/or drugs, if component (ii) is a dimeric entity due to the presence of a dimerization domain contained therein. Yet in other embodiments of the invention, the Gigabody carries up to, preferably equal to, 48 non-adenoviral peptides and/or drugs, if component (ii) is a tetrameric entity due to the presence of a tetramerization domain contained therein. Still in other embodiments of the invention, the Gigabody carries up to, preferably equal to, 60 non- Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys adenoviral peptides and/or drugs, if component (ii) is a pentameric entity due to the presence of a pentamerization domain contained therein. A further aspect of the present invention is method for producing the assembly as defined herein comprising the step of binding of components (i) and (ii). Preferably the method comprises the steps of: (a) preparing component (i); (b) preparing component (ii); and (c) binding component (i) to component (ii) or vice versa. Preferably, in case oxidative coupling residues such as Cys residues are present in component(s) (i) and or (ii) (i.e., in the latter case, preferably in component (1) of component (ii)), the production method of the present invention further includes a step of forming disulfide bonds in component (i) and/or in the assembly of components (i) and (ii) (i.e., forming disulfide bonds between oxidative coupling residues in component (i) to their counterparts in component (i) (i.e. (sub-)component (1) of component (ii)). The formation of disulfide bonds may be carried out by providing an appropriate oxidative environment either during the respective production step(s), i.e. for component (i) in step (a) and/or step (c), and/or for forming disulfide bonds between component (i) and component (ii) in step (c). Alternatively, oxidative formation of disulfide bonds may be carried out after preparation step (a), such as formation of disulfide bounds within or between, respectively, one or more polypeptides of component (i), by subjecting the Cy-residue(s)-containing intermediate product component (i) to an oxidation step. Furthermore, oxidative formation of disulfide bonds between component (i) and component (ii) can also be carried out after or during step (c). Methods for forming disulfide bonds in polypeptides are known in the art and disclosed, e.g. in Andreu, D., Albericio, F., Solé, N.A., Munson, M.C., Ferrer, M., Barany, G. (1994). Formation of Disulfide Bonds in Synthetic Peptides and Proteins. In: Pennington, M.W., Dunn, B.M. (eds.) Peptide Synthesis Protocols. Methods in Molecular Biology, Vol 35. Humana Press, Totowa, NJ, https://doi.org/10.1385/0-89603-273-6:91, and Lin Chen, Ioana Annis, George Barany in: Current Protocols in Protein Science, Disulfide Bond Formation in Peptides (2001), https://doi.org/10.1002/0471140864.ps1806s23. Appropriate kits for formation of disulfide bonds for use in the invention are also commercially available, e.g. PURExpress ^® Disulfide Bond Enhancer, New England Biolabs, Ipswich, MA, USA). Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys Steps (a) and (b) of the production method typically involve expression of the corresponding polypeptides using known methodology of molecular genetics and biotechnology. In preferred embodiments, the polypeptides of component (i) are prepared using commercially available kits, more preferably the MultiBac system, Geneva Biotech, Geneva, Switzerland. Step (c) typically involves the incubation of component (i) and (ii) under conditions allowing the binding of the components, such as appropriate buffer and pH conditions, such as preferably in a physiological buffer solution, optionally providing appropriate redox condition allowing the formation of disulfide bonds, if desired, as outlined above. Preferably, the production method invention involves in step (a) the formation of a dodecamer (i.e.12 entities) of component (i) which (sub-)step is preferably obtained when producing the polypeptides of component (i) by appropriate expression in an expression system allowing the formation of pentamers according to component (i) which preferably further assemble into virus-like particles comprising 12 entities of component (i). It is further preferred to obtain multimers of component (ii), preferably being selected from dimers, trimers, tetramers and pentamers. Further preferred is an embodiment of the production method of the invention wherein in step (c) 1 to 12 multimers, preferably selected from dimers, trimer, tetramers and pentamers, of component (ii) are bound to the dodecamer of component (i) obtained in step (a). It is evident, that the production method of the present invention may comprise further (sub- )steps such as purification of component (i) and/or (ii) before step (c) as well as one or more purification step after step (c). The production method of the present invention can, in particular in case component (ii) comprises a target-specific binding domain or target specific binding sequence such as an antigen, antibody, antibody mimetic or antibody fragment, be suitably comprise steps of selecting optimized sequences, such as preferably optimized as regards their affinity to the selected targeted sequence or domain respectively. For example, if the non-adenoviral peptide is an antigen same can be optimized or selected, respectively, for its immunological properties, in particular for eliciting an appropriate immune response. Typically, a library of candidate antigen sequences are tested and selected for optimized immune efficiency, i.e. resulting in the generation of optimized antibody formation in a suitable subject. Best- performing antigen sequences are then used as non-adenoviral peptides in the assembly of the present invention for vaccination. It is also possible to select antigens using the production method of the invention in that a multitude of different assemblies (preferably a Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys library of antigen-containing assemblies according to the invention) of the present invention are generated each comprising a different candidate antigen, which assemblies are produced according to the invention. The candidates are then used in test vaccination, typically in a suitable animal, e.g. in a rodent such as mouse, rat, hamster or canine, and best-performing antigen-presenting assemblies of the invention are selected and subsequently analyzed as regards the presented antigen(s), and, optionally, further optimization in one or more further selection rounds, typically until a, preferably pre-selected, threshold as endpoint is reached, or, in other embodiments, it is determined that the candidate sequences show no or at least not substantial improvement in comparison to the previous selection round. In the case of antibody (including antibody mimetics and antibody fragments such as nanobodies) selection, the method typically comprises generally known steps of affinity maturation such as in-silico and/or Darwinian selection procedures known in the art such as phage display or, more preferably, ribosome display (see also the Example of the present invention as outlined below in connection with the appended drawings). Furthermore, the present invention provides a pharmaceutical composition comprising the assembly as defined herein, preferably in combination with at least one pharmaceutically acceptable carrier. More preferably, the pharmaceutical takes the form of a vaccine when component (ii) comprises at least one antigen as defined herein. As used herein, the term "pharmaceutically acceptable" means approved by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in animals, and more particularly in humans. The term "carrier", as used herein, refers to a pharmacologically inactive substance such as but not limited to a diluent, excipient, surfactants, stabilizers, physiological buffer solutions or vehicles with which the therapeutically active ingredient is administered. Such pharmaceutical carriers can be liquid or solid. Liquid carriers include, but are not limited to, sterile liquids, such as saline solutions in water and oils, including but not limited to those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil and the like. Saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid carriers, particularly for injectable solutions. A saline solution, preferably a physiological saline solution, is a preferred carrier when the pharmaceutical composition is administered intravenously. Examples of suitable pharmaceutical carriers as well as other formulation aids are generally known in the art and described, e.g. in "Remington The Science And Practice of Pharmacy”, Adeboye Adejare (ed.), 23 ^rd ed., Elsevier B.V., Amsterdam, 2000. Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys Suitable pharmaceutical "excipients" include starch, glucose, lactose, sucrose, gelatine, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol and the like. "Surfactants" include anionic, cationic, and non-ionic surfactants such as but not limited to sodium deoxycholate, sodium dodecylsulfate, Triton X-100, and polysorbates such as polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65 and polysorbate 80. "Stabilizers" include but are not limited to mannitol, sucrose, trehalose, albumin, as well as protease and/or nuclease antagonists. "Physiological buffer solution" that may be used in the context of the present invention include but are not limited to sodium chloride solution, demineralized water, as well as suitable organic or inorganic buffer solutions such as but not limited to phosphate buffer, citrate buffer, tris buffer (tris(hydroxymethyl)aminomethane), HEPES buffer ([4 (2 hydroxyethyl)piperazino]ethanesulphonic acid) or MOPS buffer (3 morpholino-1 propanesulphonic acid). The choice of the respective buffer in general depends on the desired buffer molarity. Phosphate buffer are suitable, for example, for injection and infusion solutions. Especially in the context of the pharmaceutical composition being in the form of a vaccine, it is preferred that the pharmaceutical composition comprises one or mor adjuvant. The term "adjuvant" refers to agents that augment, stimulate, activate, potentiate, or modulate the immune response to the active ingredient of the composition at either the cellular or humoral level, e.g. immunologic adjuvants stimulate the response of the immune system to the actual antigen, but have no immunological effect themselves. Examples of such adjuvants include but are not limited to inorganic adjuvants (e.g. inorganic metal salts such as aluminium phosphate or aluminium hydroxide), organic adjuvants (e.g. saponins or squalene), oil-based adjuvants (e.g. Freund's complete adjuvant and Freund's incomplete adjuvant), cytokines (e.g. IL-Ιβ, IL-2, IL-7, IL-12, IL-18, GM-CFS, and INF-γ) particulate adjuvants (e.g. immuno- stimulatory complexes (ISCOMS), liposomes, or biodegradable microspheres), virosomes, bacterial adjuvants (e.g. monophosphoryl lipid A, or muramyl peptides), synthetic adjuvants (e.g. non-ionic block copolymers, muramyl peptide analogues, or synthetic lipid A), or synthetic polynucleotides adjuvants (e.g polyarginine or polylysine). The invention is also directed to the use of the inventive pharmaceutical composition in the treatment and/or prevention of infectious diseases and tumors. Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys The invention further relates to a method of treatment of infectious diseases and/or tumors comprising the step of administering an effective amount of the pharmaceutical composition or the polypeptide assembly, respectively, (hereinafter also respectively referred to “therapeutic agent”) of the invention to a subject, preferably a human subject, in need thereof. An "effective amount" or "therapeutically effective amount" is an amount of a therapeutic agent sufficient to achieve the intended purpose. The effective amount of a given therapeutic agent will vary with factors such as the nature of the agent, the route of administration, the size and species of the animal to receive the therapeutic agent, and the purpose of the administration. According to the invention, a first-in-kind polypeptide assembly vaccine was created, denoted as “ADDomer-COVID19”, displaying multiple copies of an oligopeptide sequence derived from the receptor binding motif (RBM) of SARS-CoV2. The authenticity and accessibility of the epitope displayed by in vitro immunization was assessed using Darwinian selection/evolution of antibody binders by Ribosome Display and high-resolution cryo-EM, revealing RBM epitope presentation and antibody binding at near-atomic resolution. Immunization of mice with ADDomer-COVID19 resulted in high level antibody titers that cross-react with VOCs including the currently predominating delta variant. Current COVID19 vaccines are administered using intramuscular injection by trained personnel. The present invention shows that nasal administration of ADDomer-COVID19 can be used as a powerful route for immunization against SARS-CoV2, demonstrating the superiority of the present invention over the prior art. The present inventors have also found that certain mutations of adenovirus penton base polypeptides which, in their wildtype form, do not or not efficiently form pentameric and/or, more preferably, VLP-structures (i.e. a dodecamer of pentamers) can lead to variants of such adenovirus penton base polypeptides forming or at least more efficiently forming pentameric and/or, more preferably VLP structures. As used herein, one or more of the terms “More efficiently” or “improved efficiency of” or “improved capability of” forming said structures means that, with regard to the yield of the respective structure, preferably a VLP structure, the yield of the respective structure, preferably of the VLP structure, increases at least by about 20 %, more preferably at least by about 30 %, even more preferably at least by about 50 %, most preferred by at least about 100 % in comparison to the yield of the respective structure, preferably the VLP structure, of the mutant in comparison to the yield obtained with Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys the wildtype form. In particular, the inventors have found that a particular conserved sequence in the N-terminal part of adenovirus penton base polypeptides can be altered in a way such that the resulting mutant has an improved capability of forming pentameric and/or, preferably, VLP structures. The conserved sequence is S-E-L-X wherein X13 is S or A. The present inventors have determined that, if a wildtype adenovirus penton base polypeptide wherein X13 is S does not or in low efficiency form pentameric and/or VLP structures (preferably VLP structures), a mutant adenovirus penton base polypeptide wherein X13 is A has an improved capability of efficiency form pentameric and/or VLP structures (preferably VLP structures). Vice versa, if a wildtype adenovirus penton base polypeptide wherein X13 is A does not or in low efficiency form pentameric and/or VLP structures (preferably VLP structures), a mutant adenovirus penton base polypeptide wherein X13 is S has an improved capability or efficiency form pentameric and/or VLP structures (preferably VLP structures). As used herein, the term “low efficiency” or “low capability” in forming pentameric and/or VLP structures (preferably VLP structures” as used herein preferably means that in an equilibrium of the respective reaction to form pentameric structures or, preferably, VLP structures from the starting adenovirus penton base protomer polypeptides, the molecular fraction of the respective pentameric or, preferably, VLP structures is not more than about 15 %, preferably not more than about 10 % , more preferably not more than about 5 %, even more preferably not more than about 1 %, still more preferred not more than about 0.5 %. In most preferred embodiments, the wildtype adenovirus penton base protomer polypeptide is essentially incapable of forming a pentameric or, preferably VLP structure. Therefore, the present invention is directed to a mutant adenovirus penton polypeptide capable of forming pentameric and/or VLP structures, preferably capable of forming VLP structures, said polypeptide comprising a mutation in the sequence S-E-L-X wherein X13 is S or A or C, wherein, when the wildtype of said adenovirus penton base polypeptide comprises the sequence SELA and does not form pentameric and/or VLP structures, preferably the Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys wildtype said adenovirus penton base polypeptide does not form VLP structures, the mutant adenovirus penton base polypeptide comprises the sequence SELS or SELC; and wherein, when the wildtype of said adenovirus penton base polypeptide comprises the sequence SELS and does not form pentameric and/or VLP structures, preferably the wildtype said adenovirus penton base polypeptide does not form VLP structures, the mutant adenovirus penton base polypeptide comprises the sequence SELA or SELC. Mutant adenovirus penton base polypeptides of the present invention wherein the A or S, respectively, amino acid in the wild type amino acid sequence is replaced by C have or may have the further benefit that the C in the SELC sequence is able to form or forms, respectively, a disulfide bridge with the corresponding C amino acid in the SELC motif in the neighboring penton base polypeptide in a VLP formed of such penton base polypeptides. Preferably, the mutant adenovirus penton base polypeptide of the invention is a mutant of a chimpanzee adenovirus penton base polypeptide. More preferably, the mutant of the chimpanzee adenovirus penton base polypeptide comprises the sequence SELS (i.e., the corresponding wildtype chimpanzee adenovirus penton base polypeptide comprises the sequence SELA). Further preferred is a mutant penton base polypeptide of the invention being a mutant of a chimpanzee adenovirus comprising the sequence SELC. Most preferred, the mutant adenovirus penton base polypeptide is an SELS or an SELC, the latter being even more preferred, mutant of chimpanzee adenovirus serotype Y25 (which wildtype sequence comprises the sequence SELA). A particularly preferred mutant of the present invention comprises, essentially consists of or consists of the following sequence (SEQ ID NO: 47): MMRRAYPEGP PPSYESVMQQ AMAAAAAMQP PLEAPYVPPR YLAPTEGRNS IRYSELSPLY DTTRLYLVDN KSADIASLNY QNDHSNFLTT VVQNNDFTPT EASTQTINFD ERSRWGGQLK TIMHTNMPNV NEFMYSNKFK ARVMVSRKTP NGVTVTDGSQ DILEYEWVEF ELPEGNFSVT MTIDLMNNAI IDNYLAVGRQ NGVLESDIGV KFDTRNFRLG WDPVTELVMP GVYTNEAFHP DIVLLPGCGV DFTESRLSNL LGIRKRQPFQ EGFQIMYEDL EGGNIPALLD VDAYEKSKEE SAAAATAAVA TASTEVRGDN FASPAAVAAA EAAETESKIV IQPVEKDSKD RSYNVLPDKI NTAYRSWYLA YNYGDPEKGV RSWTLLTTSD VTCGVEQVYW SLPDMMQDPV TFRSTRQVSN YPVVGAELLP VYSKSFFNEQ AVYSQQLRAF TSLTHVFNRF PENQILVRPP APTITTVSEN VPALTDHGTL PLRSSIRGVQ RVTVTDARRR TCPYVYKALG IVAPRVLSSR TF A further particularly preferred mutant of the present invention comprises, essentially consists of or consists of the following sequence (SEQ ID NO: 52): Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys MMRRAYPEGP PPSYESVMQQ AMAAAAAMQP PLEAPYVPPR YLAPTEGRNS IRYSELCPLY DTTRLYLVDN KSADIASLNY QNDHSNFLTT VVQNNDFTPT EASTQTINFD ERSRWGGQLK TIMHTNMPNV NEFMYSNKFK ARVMVSRKTP NGVTVTDGSQ DILEYEWVEF ELPEGNFSVT MTIDLMNNAI IDNYLAVGRQ NGVLESDIGV KFDTRNFRLG WDPVTELVMP GVYTNEAFHP DIVLLPGCGV DFTESRLSNL LGIRKRQPFQ EGFQIMYEDL EGGNIPALLD VDAYEKSKEE SAAAATAAVA TASTEVRGDN FASPAAVAAA EAAETESKIV IQPVEKDSKD RSYNVLPDKI NTAYRSWYLA YNYGDPEKGV RSWTLLTTSD VTCGVEQVYW SLPDMMQDPV TFRSTRQVSN YPVVGAELLP VYSKSFFNEQ AVYSQQLRAF TSLTHVFNRF PENQILVRPP APTITTVSEN VPALTDHGTL PLRSSIRGVQ RVTVTDARRR TCPYVYKALG IVAPRVLSSR TF The mutant adenovirus penton base polypeptide of the invention may comprise further mutations such as in one of the first and the second RGD loop or in both the first and the second RGD loops and/or in the V loop as disclosed in WO 2017/167988 A1 as well as disclosed herein. The mutant adenovirus penton base protomer polypeptide of the invention may further comprise one or more coupling residues as outlined above. The invention also related to a pentamer of the mutant adenovirus penton base protomer polypeptide of the invention. The invention further relates to a VLP comprising 12 pentamers of the mutant adenovirus penton base protomer polypeptide of the invention. Mutants of the invention are also denoted herein as “SELA mutant” or “SELS mutant” or “SELC mutant”. A particularly preferred assembly of the invention comprises component (i) wherein the adenovirus penton base polypeptides have the sequence of a mutant adenovirus penton base polypeptide as defined herein. Most preferred the assembly of the present invention contains, as component (i), a mutant adenovirus penton base protomer polypeptide comprising or essentially consisting of or consisting of, respectively, the sequence according to SEQ ID NO: 51. Preferred assemblies of the invention comprise as component (ii) thereof a sequence selected from SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50 and SEQ ID NO: 52. The Figures show: Fig.1: 2.2 Å Cryo-EM structure of ADDomer-COVID19 candidate vaccine. (a) SARS-CoV2, the virus that causes COVID19, shown in a schematic view. Spike glycoprotein trimers on the surface of the virus are colored in red (left). The SARS-CoV2 Spike protein is shown in a cartoon representation, with the monomers colored in blue, red Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys and magenta. The receptor binding domain (RBD) that attaches to the ACE2 receptor on the host cell surface mediating virus entry and infection is boxed in black, with the receptor binding motif (RBM) colored in red (center). The RBD is shown in a zoom in view (right, the RBM is marked). A polypeptide segment derived from the RBM was grafted on the ADDomer scaffold, into the VL insertion site, giving rise to the ADDomer-COVID19 candidate vaccine. (b) Cryo-EM structure of ADDomer-COVID19 at 2.2Å resolution is shown. The particle self- assembles from 60 copies of a an engineered protomer, each containing an RBP epitope. Promoters are colored in different colors. The particle is composed of 12 identical pentons that assemble into a dodecahedron. ADDomer-COVID19 is viewed facing a penton in this representation (left). The same particle is shown colored in gray on the right. The RBM epitopes, are colored in red. (c) Cryo-EM grids (top left), 2D class averages (bottom), and EM density (top right) are shown demonstrating the excellent quality of the data. In the EM density, individual side chains of the amino acid residues are clearly visible. (d) A penton from ADDomer-COVID19 (rainbow colored) is shown looking through the center, overlayed on the previously determined Cryo-EM structure of unmodified ADDomer scaffold (colored in blue). The central channel in the penton is less constrained in ADDomer- COVID19. It appears that a segment, structured as an alpha- helix in the previous structure, is unfolded in ADDomer-COVID19, hinting at longer range structural rearrangements translating through the structure. The structure overly is shown in more detail on the top left and on the bottom in three views showing only a protomer. The protomer from ADDomer- COVID19 is colored in green, the overlayed ADDomer scaffold promoter in blue. The helix shown in blue is unfolded in ADDomer-COVID19. Fig.2: In vitro immunization with ADDomer-COVID19 using ribosome display. (a) Darwinian in vitro selection and evolution by Ribosome Display. ADDomer-COVID19 (colored in grey, RBM epitopes colored in red) is immobilized as an antigen on a surface. Ribosome nascent-chain complexes (RNCs) are formed by in vitro coupled transcription/translation, comprising ribosomes (colored blue) linked to mRNAs (red) encoding nanobodies from a naïve synthetic nanobody library. The mRNAs lack a stop codon, therefore mRNA, and nanobody remained tethered to the ribosomes forming RNCs, thus maintaining the link between genotype and phenotype. The nanobody constructs contain a linker which allows them to fold into functional binders outside of the ribosomal tunnel. Up to10 ¹² RNCs, each presenting a different nanobody, are panned over immobilized ADDomer-COVID19 in one experiment.RNCs comprising nanobodies that do not bind are washed away. Bound RNCs are then disassembled by adding EDT and the mRNAs collected, and reverse transcribed by error-prone PCR to introduce mutations in a focused Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys library. This process is repeated iteratively. Soluble ADDomer not containing RM epitopes is added as competitor, RNCs comprising nanobodies specific for ADDomer-COVID19 are then tested by ELISA for binding to the native target (here immobilized Spike protein). Encoding genes are recovered by RT PCR, cloned into a bacterial expression plasmid and purified, yielding a selection of nanobodies binding to 94 ADDomer-COVID19. The process mimics in vitro a prime/boost regimen. An example of a purified nanobody, ADAH11, is shown(right). ADAH11elutes in a single peakin size exclusion chromatography (SEC). The corresponding SDS-PAGE gel section is shown. ADAH11 is marked with a triangle colored in black. (b) ELISA of selected nanobodies ADAH11, ADAH14 and ADAH15 is shown with immobilized antigens BSA (control), ADDomer, ADDomer-COVID19, a Spike lacking the RBM (Spike ∆RBM), Spike and the RBD. (c) ADAH11 was reacted with ADDomer-100 COVID19 in a 100:1 ratio and purified by size exclusion chromatography (SEC). The ADDomer-COVID19/nanobody complex elutes in a single peak. The corresponding SDS-PAGE gel section is 102 shown. ADAH11 is marked with a triangle colored in black. ADDomer-COVID19 is marked with an asterisk. (d) Cryo-EM grid section and 2D class averages of ADDomer-COVID19/ADAH11 complex are shown. The position of the nanobody bound to the surface of the nanoparticle can already be discerned in the class averages. (e) SARS-CoV-2 neutralization by ADAH11 using ACE2 expressing Caco-2 (left) and TMPRSS2-expressing Vero E6 cells (right). Dilutions are indicated. Fig.3: ADDomer-based picomolar affinity SARS-CoV-2 RBM binding assembly. (a) Low resolution Cryo-EM structure of Adenovirus is shown (green). The junction between virus capsid and fiber tail is boxed in black. The junction is shown in a zoom in view. The penton base from which the ADDomer was derived is colored in grey, the fiber is colored in orange. The fiber represents a trimer, due to averaging in EM the fiber is not well resolved. The penton base is also shown in a top view. Only the fiber tail peptides binding to clefts present on the penton base are shown. Five clefts exist, one per penton protomer. Only three are bound by fiber tail peptides (colored in orange), averaging generates fiber tail density on all five clefts in the EM structure. (b) Fiber tail sequences from adenovirus serotypes are depicted. The fiber tail sequences encompassing seven amino acid residues (underlaid in orange) are highly conserved. (c) Surface plasmon resonance (SPR) of ADAH11 nanobody binding to immobilized ADDomer-COVID19 presenting the RBM epitope. The monomer binds with 108 nM affinity. Concentrations ranging from 40nM to 160nM were used. Black lines correspond to a global fit of the data using a 1:1 binding model. Each experiment was repeated independently three times. All protein concentrations were used to calculate the KD value. Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys (d) ADAH11 nanobody fitted with a synthetic trimerization domain fused to a fiber tail peptide (left). Three monomers assemble into a stable trimer mimicking the natural fiber arrangement. (e) Trimer was incubated with ADDomer scaffold in a 15:1 ratio and the resulting ADDomer/ADAH11 complex (hereinafter referred to as “Gigabody”) purified. SPR analysis reveals a remarkable increase in affinity to the RBM epitope peptide (SARS-CoV-2 subtype Wuhan) presented by the candidate vaccine, which is now low picomolar. The slow dissociation indicates that the Gigabody does not release from the RBM epitope during the experiment. (f) Hydrid structure of the Gigabody based on high resolution Cry-EM, crystal structures of nanobody and trimerization domain and molecular modeling. The nanobody trimers emanating from the 12 penton bases are colored in green. (g) Laser scanning confocal microscopy images of ACE2-expressing A549 cells 2.5 hours after incubation with synthetic SARS-CoV-2 MiniVs decorated with spike glycoprotein. MiniVs were either left untreated or exposed to 500 nM nanobodies or 500 nM Gigabody for 30 min before addition to the cell cultures. Scale bar is 50 μm. (h) Quantification of MiniV retention in ACE2-expressing A549 cell monolayers 2.5 hours after incubation. Competitive binding of Gigabody to MiniV-presented spike was assessed in a serial dilution series. Graph shows mean standard deviations from three technical replicates. (i) Dynamic light scattering analysis of Gigabody-mediated MiniV aggregation. MiniVs hydrodynamic size distribution is shown for untreated controls, and MiniVs that were pre- treated with 500 nM Gigabody for 30 min, respectively. (j) SPR of ADAH11 binding to immobilized Delta (left panel) and Omicron (right panel) RBDs, at concentrations 50 nM to 250 nM for Delta, and 1 uM to 3 uM for Omicron. (k) Trimer was incubated with ADDomer scaffold in a 15:1 ratio and the resulting Gigabody complex purified. SPR analysis reveals a high affinity to the RBM epitope peptide (SARS- CoV-2 subtype Omicron) presented by the candidate vaccine, which is betweennow low picomolar. The slow dissociation indicates that the Gigabody does not release from the RBM epitope during the experiment. Fig.4: ADDomer-COVID19 in vitro immunization elucidates nasal vaccination route. (a) Depicts the homologous prime/boost protocol used for immunization of mice. (b) to (d) shows graphical representations of the immunization experiments. (e) EILSA showing serum IgG binding to immobilized wildtype SARS-CoV-2 (Wuhan) and Variants of Concern (VoCs) Alpha, Beta and Delta evidencing cross-reactivity. The present invention is further illustrated by the following non-limited example: Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys EXAMPLE Production, purification and characterization of Gigabody assembly having picomolar antigen affinity against SARS-CoV-2 variants MATERIALS AND METHODS Protein production ADDomer-COVID19 A 33 amino acid epitope (SEQ ID NO: 53) of SARS-CoV-2 receptor binding motif (RBM, SEQ ID NO: 54) was inserted into the variable loop (VL loop) of the ADDomer scaffold based on the penton base protein of human Adenovirus 3 (hAd3) as described in WO 2017/167988 A1 and Vragniau et al. (2019) Sci. Adv.5, eaaw2853; see, in particular Supplemental Material Figs. S1 and S2 and their respective legends). SARS-CoV-2 RBM: KVGGNYNYLY RLFRKSNLKP FERDISTEIY QAGSTPCNGV EGFNCYFPLQ SYGFQPTNGV GYQ (SEQ ID NO: 54) AH epitope: YQAGSTPCNG VEGFNCYFPL QSYGFQPTNG VGY (SEQ ID NO: 53) Chimpanzee-ADDomer-SELS Chimpanzee-ADDomer Chimpanzee-ADDomer-SELS was produced using the MultiBac baculovirus expression system (Geneva Biotech, Geneva, Switzerland) in Hi5 cells using ESF921 media (Expression Systems Inc.). Tn7 transposition was used to insert pACEBac-Chimpanzee- ADDomer-SELS into an engineered baculoviral genome, EMBacY, in DH10EMBacY cells. Transfection and baculovirus amplification in SF21 suspension cultures was performed following established protocols. Amplified baculovirus (V ₁ ) was used to infect Hi5 suspension cultures (~5 ml/L of Hi5 culture). The EmBacY baculoviral genome encodes a yellow fluorescent protein (YFP) marker. Once YFP expression had plateaued, the cultures were centrifuged at 1200 rpm for 10 minutes, the supernatant was discarded, and the cell pellets flash frozen in liquid N ₂ before storage at -80°C. Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys Cell pellets were fully resuspended in lysis buffer (50mM Tris pH 7.5, 150mM NaCl), supplemented with an EDTA-free protease inhibitor cocktail tablet (Roche, Basel, Switzerland)/50ml lysis buffer. Three cycles of freezing in liquid N ₂ and thawing at room temperature were used for cell lysis. The lysate was cleared from debris by centrifugation at 40,000g for 30 minutes and subsequent collection of the supernatant. Benzonase nuclease (Sigma-Aldrich, St. Louis, Missouri) and 2mM MgCl ₂ were added to the supernatant and left to incubate overnight at room temperature. The cell lysate was centrifuged at 4000g for 15 minutes and filtered (0.45 µm Millex® sterile filter unit, Merck Millipore, Burlington, Massachusetts) before loading onto a XK WorkBeads size-exclusion column (GE Healthcare, Chicago, Illinois) equilibrated in lysis buffer. Eluted fractions were analyzed by reducing SDS-PAGE and those containing Chimpanzee-ADDomer-SELS were pooled and left to incubate overnight with benzonase nuclease (Sigma-Aldrich, St. Louis, Missouri) and 2mM MgCl2. The pooled fractions were centrifuged at 4000g for 15 minutes and filtered (0.45 µm Millex® sterile filter unit, Merck Millipore, Burlington, Massachusetts) before loading onto a High Q column (Bio-Rad Laboratories, Hercules, California). Ion-exchange chromatography was performed by applying a linear salt gradient (50mM to 500mM NaCl). Fractions were analyzed by reducing SDS-PAGE and fractions containing pure Chimpanzee- ADDomer-SELS pooled. Pooled fractions were concentrated using a 50 kDa MWCO Amicon centrifugal filter unit (EMD Millipore, Burlington, Massachusetts) and buffer-exchanged in phosphate-buffered saline (PBS) pH 7.4. Ultimately, the samples were sterile filtered (0.45 µm Millex® sterile filter unit, Merck Millipore, Burlington, Massachusetts), flash frozen in liquid nitrogen and stored at -80°C. The integrity of the final sample was confirmed using both reducing SDS-PAGE and negative stain electron microscopy (EM). ADAH11_Trimer1, ADAH11_Trimer2 and ADAH11_Trimer3 Sequences codon-optimized for bacterial expression encoding the chimpanzee-derived adenovirus fiber tail peptide, the T4-foldon trimerization domain and linker sequences of variable lengths were synthesized and inserted into the pHEN6_ADAH11 plasmid at the N- terminus of the ADAH11 coding sequence (Genscript Inc, New Jersey USA). ADAH11_Trimer1, ADAH11_Trimer2 and ADAH11_Trimer3 differ in the length of linkers between the fiber tail peptide and trimerization domain (see Table 1). ADAH11_Trimer1, ADAH11_Trimer2 and ADAH11_Trimer3 were produced in the T7 Express bacterial strain (NEB) using Terrific Broth (TB) medium. TB was inoculated with overnight precultures (9ml/L of medium) and incubated at 37°C for 2 hours, before being induced with 1mM Isopropyl β- d-1-thiogalactopyranoside (IPTG). Cultures were incubated overnight at 16°C then cells were Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys harvested by centrifugation (4,000g for 10 minutes). The cell pellets were resuspended in lysis buffer (50mM Tris-HCl pH 8, 300 mM NaCl, 10 mM Imidazole, 0.5mg/mL Lysozyme) with buffer volume calculated according to OD ₆₀₀ (lysis buffer volume = culture OD ₆₀₀ x culture volume/100). Samples were frozen at -20°C, then thawed at 37°C for 10 minutes before the addition of DNase + MgSO4. Samples were incubated at 4°C for 15 minutes under rotation, then sonicated at 50% amplitude for 4x 30 seconds, Pulse 1s/1s. Samples were clarified by centrifugation (12,000g for 15 minutes) and the final supernatant loaded onto a 5ml Ni affinity column using an ÄKTAxpress system (Cytiva). The column was washed with Wash Buffer (50 mM Tris-HCl pH 8, 300 mM NaCl, 50 mM Imidazole) and the protein eluted with 1.5 cV Elution Buffer (50 mM Tris-HCl pH 8, 300 mM NaCl, 250 mM Imidazole). Fractions containing target protein were pooled and concentrated to 500 uL using a 10 kDa MWCO Amicon centrifugal filter unit (EMD Millipore). The concentrated sample was subjected to size exclusion chromatography (SEC) using a Superose 6 HR 10/30 column equilibrated with 1x PBS (pH 7.4). Peak fractions were pooled and aliquoted at the concentration found. Gibabody assembly ADAH11-Trimer 3 Gigabody was assembled by mixing purified ADAH11-Trimer 3 with Chimpanzee-Pentamer-SELS in PBS pH 7.4 at a molar ratio of 1:1.2 Chimpanzee-ADDomer- SELS penton to ADAH11-Trimer 3 trimer. After a 1-hour incubation rotating at 4°C, the mixture was subjected to SEC on a Superdex 20010/300 GL column (GE Healthcare, Chicago, Illinois) equilibrated in PBS pH 7.4. Peak fractions were run on an SDS-PAGE gel and those containing ADAH11-Trimer 3 Gigabody were pooled. The pooled samples were concentrated using a 100 kDa MWCO Amicon centrifugal filter unit (EMD Millipore, Burlington, Massachusetts) before storage at 4°C (if using immediately) or flash freezing in liquid N2 and storage at -80°C. Negative stain sample preparation and microscopy 5 µl of 0.05 mg/mL Chimpanzee-ADDomer-SELS and ADAH11-Trimer 3 Gigabody were applied to a CF300-Cu-50 grid (Electron Microscopy Sciences, Hatfield, Pennsylvania) grid following glow discharge (30s at 15 mA). The sample was incubated on the grid for 1 minute and then manually blotted.5 ul of 3% uranyl acetate was then applied to the grid for 1 minute before manual blotting. Images were recorded on a 200-kV Tecnai F20 microscope (FEI Company, Hillsboro, Oregon) equipped with a 4K × 4K Ceta camera at a magnification of 62,000x, corresponding to pixel size of 1.63 Å using the EPU software. Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys Surface plasmon resonance (SPR) experiments SPR experiments were performed on a Biacore ^® T200 (GE Healthcare, Chicago, Illinois) according to the manufacturer’s protocols and recommendations. ADAH11 nanobody binding to SARS-CoV-2 RBDs - Biotinylated RBD proteins were immobilized on streptavidin-coated SA sensor chips at ~3845 response units (RU) for Wuhan RBD (Fig. 3c) and ~2500 RU for Delta and Omicron RBD. Binders were diluted to the concentrations indicated (Fig. 3j: Delta RBD – left panel; Omicron RBD – right panel) and passed over immobilized RBDs at a flow rate of 30 µl/minute. The Running Buffer for all SPR measurements was PBS. The sensorgrams were analyzed using the Biacore ^® Evaluation Software (GE Healthcare) and kon, koff and KD values were determined using a two state reaction binding model. All experiments were performed in triplicates. Gigabody binding to WUHAN RBD - Purified, biotinylated RBD ligand was immobilized on a streptavidin-coated (SA) sensor chip (GE Healthcare, Chicago, Illinois) at 2453 response units (RUs). For all interaction measurements, the analyte was injected at a flow rate of 50 μl/min for 120s using PBS pH 7.4 as the running buffer. Dissociation was performed for 600s. ADAH11-Trimers 1-3 were serially diluted and injected at concentrations of 10nM, 20nM, 30nM and 40nM. ADAH11-Trimer 3 Gigabody and Chimpanzee-ADDomer-SELS were serially diluted and injected at concentrations of 0.5nM, 1.0nM, 1.5nM and 2.0nM. For ADAH11- Trimers 1-3, Chimpanzee-ADDomer-SELS and ADAH11-Trimer 3 Gigabody interaction measurements, the chip was regenerated using 2 injections of 10mM glycine pH 2.6. All measurements were performed in triplicate. Sensorgrams were analyzed and the raw data individually fit using a 2-state reaction binding model with the Biacore ^® Evaluation Software (GE Healthcare, Chicago, Illinois). From this, all KD, kon and koff values were determined. Final sensorgrams for ADAH11-Trimer 3 Gigabody interaction measurements were obtained by subtracting the Chimpanzee-ADDomer-SELS sensorgrams at each analyte concentration from the corresponding ADAH11-Trimer 3 Gigabody sensorgrams. This subtraction accounted for non-specific binding of the Chimpanzee-ADDomer-SELS scaffold to the sensor chip. Results of this experiment are shown in Fig.3e. Gigabody binding to OMICRON RBD – Purified, biotinylated RBD ligand was immobilized on a streptavidin-coated (SA) sensor chip (GE Healthcare, Chicago, Illinois) at 3622 response units (RUs). For all interaction measurements, the analyte was injected at a flow rate of 30 μl/min for 120s using PBS pH 7.4 as the running buffer. Dissociation was performed for 600s. ADAH11-Trimer 3 Gigabody was serially diluted and injected at concentrations of 1.0nM, Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys 1.5nM, 2.0nM and 2.5nM. Two cycles of regeneration were performed using 10 mM glycine- HCl pH2.6. Sensorgrams were analyzed and the raw data individually fit using a 1:1 binding reaction model with the Biacore ^® Evaluation Software (GE Healthcare, Chicago, Illinois). K _D , k _a and k _d values were determined from these fits. Results of this experiment are shown in Fig. 3k. SARS-CoV-2 virus neutralization assay Vero E6 cells engineered to express the cell surface protease TMPRSS2 (VeroE6- TMPRSS2) (NIBSC) (Matsuyama et al. (2020) PNAS, 117, 7001-7003) and Caco-2 cells engineered to express ACE2 (Gupta et al. (2022) Nt. Comm.13, 222) were cultured at 37°C in 5% CO2 in DMEM containing GlutaMAX (Gibco, Thermo Fisher) supplemented with 10% (v/v) FBS (Gibco) and 0.1 mM non-essential amino acids (NEAA, Sigma Aldrich). The ADAH11 nanobody was serially diluted 2-fold for eight dilutions, from a 0.85 μg/ml starting dilution, in triplicate, in Minimum Essential Media (MEM, Gibco) containing 2% (v/v) FBS and NEAA. The ancestral SARS-CoV-2 isolate hCoV-19/England/02/2020 (GISAID ID: EPI_ISL_407073) was grown on VeroE6-TMPRSS2 cells and titrated as previously described (Gupta et al. , supra). Virus (60 μl of 8 x 104 TCID50/ml) was mixed 1:1 with dilutions of ADAH11 and incubated for 60 min at 37°C. Following the incubation, supernatants were removed from Caco-2-ACE2 and VeroE6-TMPRSS2 cells seeded previously in μClear 96 well microplates (Greiner Bio-One) and replaced with 100 μl of the virus:sera dilutions followed by incubation for 18 hours at 37°C in 5% CO2. Control wells containing virus only (no ADAH11) as well as a positive control (a commercial monoclonal antibody (Absolute Antibody; Sb#15) recognizing the S protein RBD) and media only negative control were also included on each plate. Cells were fixed by incubation in 4% paraformaldehyde for 60 minutes followed by permeabilization with Triton-X100 and blocking with bovine serum albumin. Cells were stained with DAPI (Sigma Aldridge) and an antibody against the SARS-CoV-2 nucleocapsid protein (1:2000 dilution, 200-401-A50, Rockland) in combination with a corresponding fluorophore conjugated secondary antibody (Goat anti- Rabbit, AlexaFluor 568, Thermo Fisher). Images were acquired on the ImageXpress Pico Automated Cell Imaging System (Molecular Devices) using a 10X objective. Stitched images of 9 fields covering the central 50% of the well were analyzed for infected cells using Cell ReporterXpress software (Molecular Devices). Cell numbers were determined by automated counting of DAPI stained nuclei, infected cells were determined as those cells in which positive nucleocapsid staining, associated with a nucleus, was detected. The percentage of infected cells relative to control wells containing virus only (no ADAH11) were calculated. Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys SARS-CoV-2 MiniV preparation Artificial minimal SARS-CoV2 virions (MiniVs) were assembled from small unilamellar vesicles (SUVs) as described previously (Zubieta et al. (2005) Mol. Cell 17121-135). Briefly, MiniVs were incubated with A549 cells at a final lipid concentration of 10 μM in flat bottom 96 well plates and in low serum containing culture medium (DMEM supplemented without phenol red, 4.5 g/l glucose, 1% L-glutamine, 1% penicillin/streptomycin, 0.01 mg/mL recombinant human insulin, and 0.5% fetal bovine serum). After 2.5 hours, MiniV Rhodamine B fluorescence was measured with a plate reader for each well in 4 positions. Cultures were afterwards washed 3 times with PBS. Subsequently, residual fluorescence was measured in each well and normalized to the initial fluorescence intensity to calculate MiniV retention values after correction for background fluorescence and negative controls. Gigabody dilution curves for retention analysis were prepared by preincubating MiniVs with 500 nM Gigabody for 30 min at 4°C in the dark before addition to the cells for retention analysis. Mouse immunization experiments Female C57BL/6 mice were obtained from Charles River Laboratories (UK) and maintained at the University of Bristol Animal Services Unit in specific pathogen-free conditions in accordance with established practices and under a UK Home Office License (Morgan et al. (1996) J. Immunol.157, 978-983). Mice were immunized with 40μg ADDomer-COVID19 vaccine or ADDomer scaffold as a control via intra-nasal, intramuscular or subcutaneous routes (n = 10 mice per treatment group pooled across 2 experimental replicates) on day 0 (primary immunization), day 21 (boost 1) and day 42 (boost 2). Mice were humanely euthanized on day 62; 9 weeks post initial immunization, by terminal exsanguination under general anesthesia. Intranasal (IN) Mice were lightly anaesthetized using isoflurane, and 12.5μL ADDomer-COVID19 accine in sterile PBS (1.6mg/mL) was instilled into each nostril (total dose 25μL; 40μg). Intramuscular (IM) Mice were lightly anaesthetized using isoflurane and received intramuscular injection with 50μL ADDoCoV vaccine in sterile PBS (0.8mg/mL) into the quadriceps muscle using a 25G 5/8 inch needle (total dose 50μL; 40μg). Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys Subcutaneous (SC) Non-anaesthetized mice were restrained in a tube restrainer. Subcutaneous injection was performed with 50μL ADDoCoV vaccine in sterile PBS (0.8mg/mL) using a 25G 5/8 inch needle at the tail base (total dose 50μL; 40μg). Sample collection The presence of serum antibody was assayed in peripheral blood at baseline (day -1), day 20, and day 41 and in terminal bleeds on day 62. Peripheral blood samples (30- 50μL) were collected from the lateral tail vein. For collection of terminal blood samples, mice were deeply anesthetized using isoflurane, and 500-800μL of blood was collected following thoracotomy and cardiac puncture. Peripheral blood and terminal bleed samples were processed for serum collection. Blood was collected into autoclaved microcentrifuge tubes without anti-coagulant and allowed to clot at room temperature for 20 minutes. Samples were centrifuged at 2000 g for 10 minutes at 4oC. Serum was transferred to a fresh microcentrifuge tube, and centrifugation was repeated at 2000 g for 10 minutes at 4oC. Following centrifugation, serum was transferred to a fresh microcentrifuge tube and frozen in aliquots at -80 °C. Nasal washes (NW) and bronchoalveolar lavages (BAL) were taken post- 704 mortem using established methodology (Cisney et al. (2012) J. Vis. Exp.3960; Van Hoecke et al. (2017) https://doi.org:10.3791/55398). The presence of mucosal antibody in murine nasal secretions were assayed by flushing a 500μL volume of ice-cold PBS through the nasal turbinates. Briefly, scissors were used to make an incision from the abdomen to the jaw in order to expose the thoracic cage and neck. The trachea was exposed and a 20G x32mm Surflo intravenous catheter (VWR international) inserted. A 1mL syringe containing 500μL PBS was then attached and the fluid used to flush the nasal cavity. Fluid existing the nares was captured using an Eppendorf and then incubated on ice with Protease inhibitor cocktail (Roche Diagnostics, Darmstadt, Germany). Washes were centrifuged at 1000 g for 10 minutes at 4oC to remove cellular debris and mucus. Fluid supernatants were transferred to fresh autoclaved microcentrifuge tubes and immediately frozen in aliquots at -80 °C. To isolate mucosal antibody in the lower respiratory tract, lung lavages were performed. Briefly, the catheter was withdrawn and inserted, pointing towards the lungs. A syringe containing 1mL ice-cold PBS was used to aspirate the lungs, ensuring not to overinflate and Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys rupture the tissue. To prevent PBS from leaking from the catheter insertion site, thread was used to tie off the catheter to the trachea. Recovered PBS from lung washes were again incubated on ice with protease inhibitor then centrifuged at 1000 g for 10 minutes at 4oC to remove cellular debris and mucus (Mann et al. (201) J. Control. Release 170, 452-459). Fluid supernatants were transferred to fresh autoclaved microcentrifuge tubes and immediately frozen in aliquots at -80 °C. RESULTS Self-assembling thermostable ADDomer-based COVID19 candidate vaccine ADDomer- COVID19 The SARS-CoV-2 virion surface is decorated by S, a trimeric glycoprotein mediating cell attachment and infection (Wrapp eta .. (2020) Science 367, 1260-1263; Walls et al. (2020) Cell 181, 281-282 e 286; Toelzer et al. (2020) Science 370, 725-730). Each S monomer contains a receptor binding domain (RBD) comprising the receptor binding motif (RBM). In the open form adopted by S, the RBM is positioned to interact tightly with the cellular receptor, angiotensin converting enzyme 2 (ACE2) (Fig.1a). According to methods as described in WO 2017/167988 A1, an epitope (“AH”; SEQ ID NO: 53) encompassing 33 amino acids of the SARS-CoV-2 Wuhan RBM (SEQ ID NO.54) in between residues Y505 and Y473 was inserted into the variable loop (VL) of the Chimpanzee SELS penton base protein. AH containing penton base protein was produced following the protocol in Sari-Ak et al. (2021) Curr. Protoc.1, e555, resulting in highly purified ADDomer-COVID19 adopting the dodecahedral structure. The cryo-EM structure of ADDomer-COVID19 was determined at 2.2 Å resolution (see Fig.1c). ADDomer-COVID19 contains 60 AH epitopes exposed on the nanoparticle surface in flexible loops, available for antibody binding (Fig.1b). In vitro generated SARS-CoV-2 neutralising nanobody binders by Ribosome Display The rationale for the ADDomer-COVID19 vaccine design is to elicit antibodies that can bind the RBM, and thus prevent SARS-CoV-2 attachment to ACE2, neutralising the virus. A prerequisite for this is authenticity and accessibility of the AH epitope in the context of the ADDomer-COVID19 nanoparticle. To validate our design, Ribosome Display was used to select antibody binders from a naïve synthetic nanobody library, with ADDoCoV as an antigen (Fig.2a). In Ribosome Display, a DNA library encoding for nanobodies is transcribed and translated in vitro (Schaffitzel et al. (2005) In vitro Selection and Evolution of Protein- Ligand Interactions by Ribosome Display.. In: Protein-Protein Interactions: A Molecular Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys Cloning Manual.2nd edition. Eds: E. Golemis & P. Adams, Cold Spring Harbor Laboratory Press, New York. Chapter 27). In the library, the stop codons are deleted and replaced with a DNA sequence encoding an oligopeptide spacer. Thus, in vitro transcription and translation gives rise to ribosome nascent chain complexes (RNCs) coupling the genotype (mRNA) to the phenotype (nanobody), tethered to the ribosome. RNCs comprising specific nanobody binders are selected by panning on ADDoMER-covid!) immobilized on a surface. After washing away unbound RNCs, the remaining mRNA is recovered by dissociating the bound RNCs. Reverse transcription and PCR regenerates a DNA pool enriched for specific nanobody binders. (Fig.2a). By ELISA, nanobodies were identified that bound ADDoCoV as well as SARS-CoV-2 S and RBD, but not bovine serum albumin (BSA), ADDomer, and S lacking the AH epitope (Fig.2b). A nanobody identified in this way, ADAH11, showed efficient virus neutralization in live SARS-CoV-2 assays using two different ACE2-expressing cell lines (Caco-2-ACE2 and VeroE6-TMPRSS2) (Fig.2e). ADAH11 was expressed and purified to homogeneity and tested for binding to highly purified ADDoCoV by SEC confirming complex formation (Fig.2c). Purified ADDoCoV-ADAH11 complex was analyzed by cryo-EM. Comparison of reference-free 2D class averages of ADDoCoV-ADAH11 or ADDoCoV, respectively, clearly indicated additional density for the nanobody containing complex (Fig.2d). By using surface plasmon resonance (SPR) using Biacore ^® (Cytivia Europe GmbH, Freiburg Germany), ADAH11 binding to the SARS-CoV-2 S RBD (subtypes Wuhan, Delta and Omicron) was characterized. ADAH11 bound immobilized S RBD Wuhan and Delta showed a low nanomolar affinity with a KD of 108 nM for the Wuhan subtype (Fig. 3c) and 59 nM for the Delta subtype (Fig.3j, left panel). Omicron S RBD, in contrast, was bound significantly less tightly as shown by a KD of 2.4 mM (Fig.3j, right panel). Of note, ADAH11 binding to Wuhan and Delta S would juxtapose R105 in CDR3 with a glutamine residue in the RBMs.. In Omicron, in contrast, this glutamine is mutated to arginine as shown by the following comparison of the epitope sequences (residues of the sequence of SEQ ID NO: 60 mutated in SEQ ID NO.61 are highlighted in bold): Epitope (partial) sequence of S RBD Wuhan and Delta, respectively: NGVEGFNCYFPLQSYG (SEQ ID NO: 60; section of sequence bound by ADAH11 underlined) Epitope (partial sequence of S RBD Omicron: NGVAGFNCYFPLRSYG (SEQ ID NO: 61; section of sequence bound by ADAH11 underlined) Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys The resulting juxtaposition of two positively charged arginine residues in RBM and CDR3 could thus contribute to significantly reduced binding of Omicron S RBD by ADAH11. In summary, a nanobody specific for an epitope derived from the RBM in the SARS-CoV-2 RBD was selected by Ribosome Display from a naïve nanobody library. This in vitro generated nanobody bound ADDomer-COVID19, cross-reacted with the RBM in SARS-CoV- 2 S, and neutralized live SARS-CoV-2 in cell-based assays, validating the authenticity and accessibility of the RBM-derived AH epitope displayed on the ADDomer-COVID19 nanoparticle vaccine. ADDomer-based ultrahigh-affinity Gigabody displaying SARS-CoV-2 nanobody binders In adenovirus, the penton represents the base for attachment of the adenoviral fibre proteins that form characteristic protrusions at the vertices of the adenoviral capsid. The fibre adopts a trimer of three identical fibre proteins. Attachment to the penton base is mediated by a highly conserved, proline- and tyrosine-rich N-terminal fibre tail peptide present on each of the monomers (Fig.1b; FNPVYPF – SEQ ID NO: 58, FNPVYPY – SEQ ID NO: 59). The fibre tail peptide binds to a tailormade fibre tail peptide-binding cleft on the penton base. In a previously reported crystal structure of an adenoviral penton bound to isolated fibre tail oligopeptides, all five binding clefts were occupied (Zubieta et al. (2005) Mol. Cell 17, 121- 235). In the adenovirus, binding of the trimeric fibre to the penton base will result in two of five clefts remaining unoccupied. The nanobodies selected by Ribosome Display neutralized live SARS-CoV-2, most likely by blocking interactions with the ACE2 receptor due to steric hindrance. The nanobodies obtained in this way were characterized by binding affinities of about 100 nM to their target antigen. ). Multimerization can enhance binding by increasing avidity (e.g. IgG, IgM), resulting in much tighter binding. For exploiting the principles of adenoviral fibre attachment nanobody ADAH11 was used as a starting point, with the aim of creating the ultra-high affinity superbinder according to the invention, hererin referred to as !Gigabody”, displaying multiple copies of ADAH11, with the potential to forestall SARS-CoV-2 infection, which conceivably, could be utilized for passive immunization. ADDOmer-COVID19 based on a penton base protomer derived from human adenovirus serotype Ad3, which can efficiently self-assemble into a dodecahedron (Vragniau et al.2019, supra).. For the Gigabody according to the present Example, the penton base protomer, derived from chimpanzee adenovirus Ad25. Using the adenovirus fibre as a blueprint, a Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys nanobody trimer was designed by fusing a T4 phage derived trimerization domain (T4 foldon) preceded by the AdY25 fibre tail, to the N-terminus of ADAH11 (see Fig.3d). In the next step, the Gigabody of the present Example was produced by mixing the trimers with AdY25- derived ADDomer, purified by SEC and dodecahedron formation confirmed by negative-stain EM. Due to the 3:5 symmetry mismatch of ADAH11 trimer and penton, the trimer structure cannot be resolved at high resolution by cryo-EM, and computational modeling was used to illustrate the geometry of the Gigabody nanoparticles (Fig.3f). Fully occupied Gigabody presents 36 ADAH11 nanobodies arranged in 12 trimers, which should substantially increase binding to the cognate AH epitope by increasing avidity. Gigabody binding to SARS-CoV-2 Wuhan S RBD was tested by SPR. Binding improved enormously, from about 100 nM for momomeric ADAH11 to picomolar for the Gigabody, driven by very slow dissociation (Fig. 3e). The capacity of Gigabody to abrogate virion attachment to ACE2 expressing cells was tested. the synthetic minimal SARS-CoV-2 virions decorated with highly purified S glycoproteins (SARS-CoV-2 MiniVs) was used as a model system, affording complete control of experimental parameters (Staufer et al. (2022) Nat. Commun.13, 868; https://doi.org:10.1038/s41467-022-28446-x). SARS-CoV-2 MiniVs faithfully recapitulate viral attachment and can be studied in a regular laboratory setting (biosafety level 1), in contrast to live virus. Competitive binding of Gigabody to MiniV-presented S in a serial dilution (Fig. 3h) was assed and attachment of SARS-CoV-2 MiniVs to ACE2-expressing A549 cells exposed to Gigabody was analyzed by laser scanning confocal microscopy (Fig.3g). A auantitative inhibition of SARS-CoV-2 MiniV cell attachment at a Gigabody concentration of 1.6 nM was observed (Fig.3i). Previously, an EC50 of ADAH11 nanobody in terms of MiniV retention as 117 nM was found (Staufer et al. (2022), supra). In contrast thereto, the EC50 of the Gigabody according to the present Example is 42 pM (Fig.3h), which is 300-fold lower, closely mirroring the respective binding properties of single nanobody and Gigabody, respectively, in SPR measurements (Fig 3e). Due to the presence of multiple nanobody trimers bound to the pentons, the Gigabody assembly of the present invention is expected to induce virion aggregation, similar to agglutination. The hydrodynamic size distribution of SARS-CoV-2 MiniVs was analyzed by dynamic light scattering and an aggregation following Gigabody addition, with particle sizes increased to ~1000 nm from the diameter of a single virion (~100 nm) (Fig.3i), was confirmed. Taken together, the design of the adenoviral fibre, and its attachment mechanism in the adenovirus was mimicked to generate the Gigabody nanoparticle assembly of the invention which is decorated with multiple copies of trimerized ADAH11. By avidity, Gigabody binds the Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys cognate target in the RBM of SARS-CoV-2 S with greatly enhanced, picomolar affinity (cf. Fig.3e) as compared to nanomolar binding by ADAH11 nanobody alone (see Fig.3c). Moreover, it has been found according to the present invention that the Gigabody assembly binding to the RBMs in Wuhan S and Omicron S is virtually identical (cf. Fig.3e (Wuhan) and Fig.3k (Omicron)), while ADAH11 alone binds Omicron with significantly reduced affinity (cf. Fig.3j, right panel) as compared to Wuhan (see Fig.3c) and Delta (see Fig.3j, left panel) presumably due to the mutations accrued by Omicron in the RBM. Importantly, the Gigabody assembly of the invention effectively abolishes attachment of SARS-CoV-2 MiniVs in cell- based assays and can mediate virion agglutination. Intriguingly, Gigabody thus represents an attractive avenue for passive immunization, based on the same scaffold (ADDomer) used for ADDomer-COVID19 according to the invention, exploiting assembly principles of the adenovirus from which ADDomer was derived, and utilising antibody binders generated in vitro against ADDomer-COVID19 used as an antigen. ADDomer-COVID19 immunization experiments in vivo in mice Traditional routes of vaccine administration, such as intramuscular (IM), subcutaneous (SC) and intradermal vaccination, generally induce significant concentrations of antigen-specific IgG that are detectable in the recipient’s serum. In the present example the traditional IM or SC vaccination with intranasal (IN) vaccination was compared as this route may also induce strong systemic responses as well as significant levels of antigen-specific antibody detectable in mucosal secretions. The present inventors hypothesized that IN vaccination might be beneficial for a SARS-CoV-2 vaccine, as it could increase front-line mucosal defences against a pathogen that infects the respiratory tract and thus impact on viral transmission more effectively than the vaccines currently in use. Therefore, the immunogenicity of ADDomer-COVID19 was tested using a homologous prime-boost protocol (s. Fig.4a). Specifically, the immunogenicity of ADDomer-COVID19 in mice as compared to the naïve ADDomer nanoparticle as a control, when administered via SC, IM and IN routes, was tested. As shown (Fig.4, first, second and third panel from the left), after the vaccine prime, the ADDoCoV formulation resulted in 100% seroconversion (n = 10 mice/group) regardless of the route of administration. Elevated concentrations of anti-RBD specific serum immunoglobulin-G (IgG) were detected during study weeks 3, 6 and 9. When compared to baseline, anti-RBD IgG antibody titres in serum in week 9 after vaccination were significantly increased across all conditions (****p≤0.0005) (Fig.4, right most panel). Given the important role that immunoglobulin A (IgA) plays in defence against mucosal pathogens (Forcosi et al. (2022) Viruses 14, 187; https://doi.org:10.3390/v14020187. PMID: Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys 35215783), the serum anti-RBD IgA response after ADDomer and ADDomer-COVID19 vaccination was measured. Detectable anti-RBD IgA was also induced in serum (Fig.4c, first, second and third panel from the left), however, the IgA response developed more slowly than the IgG response, with anti-RBD IgA antibody only being significantly elevated at week 9 in the SC and IN groups compared to the week 1 baseline control (Fig.4c, right most panel). Importantly, only the IN group showed 100% seroconversion after ADDomer- COVID19 administration, with the IN routes also resulting in the highest anti-RBD IgA response in serum. Taken together, these data according to the present Example show that the ADDomer-COVID19 vaccine is immunogenic and elicits antigen-specific antibody responses in serum of vaccine recipients, irrespective of the route of administration. However, the magnitude, kinetics and isotype of the elicited antibody response are influenced by the route of administration. To gain a more in-depth understanding of the elicited antibody response after SC, IM and IN vaccination with ADDoCoV at the end of the study, nasal (Fig.4d, first and second panel from the left) and lung washes (Fig.4d, third and fourth panel from the left) were harvested to quantify the elicited anti-RBD IgG and IgA responses in mucosal secretions. As expected, systemic routes of vaccination failed to induce detectable anti-RBD IgG and IgA responses in nasal secretions with only the IN administration of ADDoCoV resulting in significantly elevated concentrations of IgG (*p≤0.05) and IgA (***p≤0.0005) compared to the ADDomer control vaccine. Interestingly, a distinct pattern of anti-RBD antibody induction was observed in lung washes. Here it was found that significant levels of anti-RBD IgG was induced regardless of the route of vaccine administration. However, despite the IM, SC and IN groups all having significant levels of anti-RBD in lung washes, it should be noted that the IN group had the highest. Interestingly, only in the IN group were significant levels of anti-RBD IgA induced in lung washes (Fig.4, right most panel). Taken together these results suggest that IN immunization may induce mucosal antibody responses more efficiently than systemic routes of administration and support the use of this route of administration to enhance interruption of acquisition and onward transmission of infection. Next, it was evaluated whether the antibodies induced by ADDoCoV vaccination were cross- reactive against a range of clinically relevant SARS-CoV-2 variants (Wuhan, Alpha, Beta, Delta, and Omicron) which would be important for broad protection, given the rapid and continuing evolution and diversification of SARS-CoV-2 in the human population. IgG antibodies induced following both IM and IN administration of the vaccine bound all SARS- CoV-2 S RBDs tested, with close to identical binding observed to Wuhan, Alpha and Delta RBDs, and reduced binding observed for Beta and Omicron RBDs (Fig.4e, left and right Habermann, Hruschka & Schnabel Patentanwälte ^ European Patent and Trade Mark Attorneys panel). Of note, a reduction in binding to Omicron RBD, as compared to Wuhan and Delta RBDs, was also observed for ADAH11, the nanobody generated by Ribosome Display, suggesting that the in vitro selection according to the invention may reproduce some of the antibody binding characteristics likewise occurring in vivo. Sequences of components of Gigabody