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2A Pharma’s vaccine platform is based on mutated parvoviral particles consisting essentially of one protein. The particles contain no viral genome and are replicative defective and non-pathogenic. Peptide sequences can be genetically inserted in two sites, allowing us to generate monovalent or bivalent vaccines as required.

Structured parvoviral particles of VP3 protein and repetitive presentation of epitopes

G VP1 VP1 VP2 VP2 VP3 VP3
VP3 G 587 453

Illustration of wild type AAV2

Illustration of AAVLP

Mutated parvovirus structural protein-based virus-like particles (VLPs) have been shown to be suitable vaccine candidates. However, for clinical development of vaccines based on VLPs, the product should ideally be based on a single active compound/protein and be as pure as possible. This presents a limitation for VLPs as viruses are often composed of more than one protein and are capable of packaging viral or host cell DNA. Wild-type parvovirus capsids are composed of three structural proteins, VP1, VP2 and VP3 in the ratio 1:1:8. Prior to the invention of 2A Pharma’s AAVLP platform, there were several attempts to generate capsids without VP1 and VP2, but the results were generally not suitable as vaccine candidates. This was either due to the expression of Rep protein – not only a second protein in a structure which should ideally be composed of only one protein, but also associated with packaging of virus genomes and unspecific DNA – or as the yield of pure VLPs from the process was too low for economical production of vaccines.

2A Pharma’s AAVLP platform has overcome these challenges by enabling the production of parvoviral particles consisting essentially of VP3, with essentially no VP1, VP2 or Rep proteins. Peptides up to 34 amino acids can be genetically inserted at the preferred sites in the VP3 capsid protein and particles can be successfully assembled with repetitive presentation of epitopes on the surface of the capsid, which induces and enhances the specific humoral immune response against the peptides. This approach enables generation of vaccines against linear B-cell epitopes.

Generate vaccines without knowing antigen or antibody binding

An alternative approach, mimotope selection, is also part of the 2A Pharma technology platform. Based on monoclonal antibodies or cellular targets delivered by a partner or from the public domain, an AAVLP displaying specific B-cell mimotopes can be selected from our library of more than 109 particles. This allows generation of vaccines – without knowing antigen or antibody binding interaction – against linear B-cell epitopes as well as against complex (discontinuous) conformational B-cell epitopes.