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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. The particle capsid surface has repetitive, immunogenic sites, where peptides of interest can be inserted and allows us to generate monovalent or bivalent vaccines as required. Each peptide of interest will be presented 60 times on the capsid surface and both the innate and adaptive immune systems are activated to produce high neutralizing antibody titers against the selected, capsid presented epitopes,

PARTICLES OF VP3 PROTEIN

STRUCTURED PARVOVIRAL PARTICLES OF VP3 PROTEIN AND REPETITIVE PRESENTATION OF EPITOPES

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. 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 with the risk of being pathogenic. 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 only of the VP3 protein, with essentially no VP1, VP2 or Rep proteins, that assembles into empty capsids. Further, peptides up to 34 amino acids can be genetically inserted at two specific 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 enable us to generate immunogenic vaccines against linear B-cell epitopes.

Illustration of wild type AAV2

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Illustration of AAVLP

GENERATE VACCINES WITHOUT KNOWING ANTIGEN OR ANTIBODY BINDING

STRUCTURED PARVOVIRAL PARTICLES OF VP3 PROTEIN AND REPETITIVE PRESENTATION OF EPITOPES

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 mimotope can be selected from our library of more than 10^9 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.

BREAK DOWN

Step 1

Identification of clinically relevant monoclonal anitobdy

AAV2 library

Screening of the AAV2 Library(3 to 4 rounds) with selected AAV2 candidates

Step 2

In-vitro selection of AAV2 candidates from library (panning)

Eliciting polyclonal antibodies

Step 3

Immunisation with selected AAV2 candidates

Polyclonal antibodies recognise original epitope on antigen

Step 4

Analysis of in-vivo antibody response and final selection of candidate