274960 Stability and Immunogenicity of H5N1 Hemagglutinin Antigens Upon Sustained Release From Polyanhydride Nanoparticles
Respiratory pathogens, including influenza, have largely increased in occurrence over the last decade. Specifically, highly pathogenic avian influenza, or H5N1 avian influenza, is becoming a contributor to these incidents with a reported 60% mortality rate among confirmed cases and growing resistance to antiviral treatments. With the potential of the virus to mutate to allow human to human transmission and develop into a global pandemic and/or a biodefense agent, it is necessary to design novel vaccines for H5N1 prevention.
Polyanhydride nanoparticle vaccines have shown efficacy in eliciting protection against intranasal pathogens. These copolymers, consisting of sebacic acid (SA), 1,6-bis-(p-carboxyphenoxy) hexane (CPH), and 1,8-bis-(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG), promote protein stability by reducing aggregation and exposure to acidic polymer degradation products. Amphiphilic polyanhydride nanoparticles also provide the ability to tailor the release kinetics of stable antigens through their amphiphilic monomers and a combination of surface and bulk erosion. Finally, polyanhydrides have been observed to have immunomodulatory capabilities, which can be harnessed to design vaccines against viral pathogens.
Previously, we have studied the stability of the H5N1 HA antigen under slightly acidic environments, which correlates strongly with the pH of polyanhydride copolymers. In this current work, we have determined the stability and release of both monomeric and trimeric forms of encapsulated HA antigens from polyanhydride nanoparticles of different chemistries. During the course of one month, released protein was quantified and examined for structural stability and functional capacity, such as the ability of HA to bind sialic acid residues and inhibit virus neutralizing antibodies. These studies identified several polyanhydride nanoparticle formulations that stabilize HA antigens. Currently, in vivo studies to examine the efficacy of these nanoparticle formulations as compared to traditional adjuvants or immunostimulatory excipients are ongoing, as well as observing the differences between monomeric HA or HA stabilized in the native trimeric state.
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