Immune response and protective efficacy of the S particle presented rotavirus VP8* vaccine in mice

Abstract

Rotaviruses cause severe diarrhea in infants and young children, leading to significant morbidity and mortality. Despite implementation of current rotavirus vaccines, severe diarrhea caused by rotaviruses still claims ∼200,000 lives of children with great economic loss worldwide each year. Thus, new prevention strategies with high efficacy are highly demanded. Recently, we have developed a polyvalent protein nanoparticle derived from norovirus VP1, the S particle, and applied it to display rotavirus neutralizing antigen VP8* as a vaccine candidate (S-VP8*) against rotavirus, which showed promise as a vaccine based on mouse immunization and in vitro neutralization studies. Here we further evaluated this S-VP8* nanoparticle vaccine in a mouse rotavirus challenge model. S-VP8* vaccines containing the murine rotavirus (EDIM strain) VP8* antigens (S-mVP8*) were constructed and immunized mice, resulting in high titers of anti-EDIM VP8* IgG. The S-mVP8* nanoparticle vaccine protected immunized mice against challenge of the homologous murine EDIM rotavirus at a high efficacy of 97% based on virus shedding reduction in stools compared with unimmunized controls. Our study further supports the polyvalent S-VP8* nanoparticles as a promising vaccine candidate against rotavirus and warrants further development.

Keywords: Nanoparticle; Norovirus; Rotavirus; S particle; Subunit vaccine; Subviral particle; Vaccine platform.