Novel nanoparticle based vaccine against respiratory viruses

Abstract

Subunit or DNA vaccines are generally less immunogenic than whole organism vaccines. One approach to reduce this deficiency is the development of repetitive antigen displays. One of the most successful repetitive antigen displays is our Self-Assembling Protein Nanoparticle (SAPN) technology. Based of coiled-coil oligomerization domains our SAPNs can self-assemble into spherical particles that mimic the size and shape of small viruses, decorated on their surface with antigens. We have used SAPNs to develop avian influenza (AI) and infectious bronchitis virus (IBV) vaccines by displaying the two conserved and antigens of these viruses. In case of AI, these M2e and Helix C in their native tetrameric and trimericoligomerization states, respectively, while B cell epitopes derived from the second heptad repeat (HR2) region of the IBV spike protein are repetitively presented in their native trimeric conformation. In addition, flagellin been co-assembled into the SAPN to achieve a self-adjuvanting effect. Specific Pathogen-Free Chickens vaccinated with such self-adjuvanted SAPNs induce significantly higher levels of antibodies than unadjuvanted SAPNs. Antibodies from chickens vaccinated with the self-adjuvanted SAPNs are cross neutralizing towards group 1 influenza strains in in vitro experiments. Immunization with self-adjuvanted SAPNs provides full protection against lethal human influenza challenge in mice, while, chickens were partially protected against a lethal pathogenic avian influenza. The IBV-SAPN vaccine fully protected chickens against pathogenic IBV. Thus, we have generated self-adjuvanted SAPNs with a great potential as universal human and avian influenza as well as IBV vaccines. Future studies are in progress to improve those SAPN-vaccines and test for crossprotection against various sub or serotypes of influenza and IBV.