A Self-Assembling Polypeptide Nanoparticle Vaccine for Avian Influenza

Abstract

While many influenza vaccines offer protection in high percentages, they have not been able to achieve optimal protectivity. M2 is a tetrameric influenza protein, found in small numbers on the viral surface, but very common on the surface of infected cells. The external domain of M2 is a highly conserved sequence and has been shown to generate a protective immune response when presented in a tetrameric conformation.Recently, we have shown that Self-Assembling Polypeptide Nanoparticles (SAPNs) are capable of eliciting a humoral immune response against a B cell epitope displayed on their surface (Kaba 2009). The basic architecture of a SAPN is an icosahedral structure composed of a linear peptide containing two coiled-coil oligomerization domains, connected by a short linker region. One of these domains is trimeric and has been de novo designed. Another can be either pentameric or tetrameric. The system can include both B-cell and T-cell epitopes, affixed to either the N- or C- terminal end.In this study, we have developed several species of SAPNs. Animal testing was performed in chickens, who received three vaccinations of M2e SAPNs. Blood samples were collected pre and post-vaccination and antibody titers were evaluated using ELISAs against different conformations of M2e. We will report on the biophysical properties of these particles and discuss their immunogenicity and potential for the design of an avian flu vaccine.