Norovirus P Particle as a Platform for Antigen Presentation

Abstract

The norovirus P particle, a subviral particle (∼20 nanometers in diameter) formed by 24 protrusion (P) domains of the norovirus capsid protein, is easily made, stable, and highly immunogenic and thus an excellent vaccine candidate against noroviruses. Each P domain has three surface loops that have been shown useful for antigen presentation. We have successfully inserted a number of small (5 aa) to large (238 aa) antigens into these loops without affecting P particle formation and production. Increased immune responses were demonstrated by improved antibody titers induced by the P particle presented antigens compared to free antigens. Significantly increased neutralization of virus and/or protection against influenza virus and rotavirus challenges have also been demonstrated in mice after immunization with chimeric P particle vaccines containing flu M2e and rotavirus VP8 antigens, compared to free M2e and VP8 antigens, respectively. The chimeric P particle-induced antibodies also blocked binding of noroviruslike particles (VLPs) to histo-blood group antigen (HBGA) receptors, indicating a potential dual vaccine against norovirus in addition to rotavirus and influenza virus. Taken together, the P particle appears to be an excellent platform for antigen presentation for vaccine development. The multiple surface loops and the large capacity of foreign antigen insertion suggest that this platform may have a wide application in vaccine development against different infectious diseases.