(139d) Stability and Release of H5N1 Hemagglutinin Antigens Encapsulated In Polyanhydride Nanoparticles

Avian influenza A H5N1 is a respiratory viral pathogen that has the potential to be the next influenza pandemic threat. Human cases of H5N1 have proven to be approximately 60% fatal with a growing number of strains becoming resistant to medical treatments. At this point in time, the infection of H5N1 is mainly spread from avian species to humans and rarely from humans to humans. However, due to the H5N1 strain’s ability to achieve rapid viral mutations, it is believed that human-to-human transmission of the virus may be coming in the near future, unleashing a possible global influenza pandemic. Therefore, there is a strong need to prepare for the prevention of H5N1 through vaccine technology.

Recombinant proteins are a new alternative in pandemic vaccines; however, they require adjuvants to enhance their immunogenicity. There are very few vaccines containing adjuvants available and licensed for human use, but the increasing ability to produce safe, purified, yet fragile and less immunogenic protein antigens calls for a need to design novel vaccine adjuvants. Biodegradable polymers have been explored as novel adjuvants with one of the most prominent class being polyesters. These polymers exhibit bulk erosion leading to exposure of the protein antigen to both water and acidic degradation products which can cause protein aggregation and degradation. Another class of biodegradable polymers, polyanhydrides, has shown potential for releasing stable protein antigens from nanoparticles. Polyanhydrides exhibit surface erosion and contain less acidic degradation products that preserve protein structure and function upon release. In this work, we have studied the release and stabilization of a recombinant H5N1 hemagglutinin (HA) from polyanhydride nanoparticles composed of sebacic acid (SA), 1,6-bis(p-carboxyphenoxy) hexane (CPH), and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG). Our results indicate that encapsulation of H5N1 HA antigen into amphiphilic nanoparticles based on CPTEG and CPH leads to stability thus retaining the antigenicity and biological function, in addition to providing sustained antigen release, which is vital to an induction of an immune response. These results are promising first steps in the development of an intranasal single dose vaccine against avian influenza.