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Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
Immune response and protective efficacy of the S particle presented rotavirus VP8* vaccine in mice
Ming Xia1, Pengwei Huang1, Xi Jiang2
1Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Insights
A novel nanoparticle vaccine candidate (S-VP8*) effectively protected mice against rotavirus challenge. This promising rotavirus vaccine strategy demonstrated high efficacy, reducing virus shedding and supporting further development.
Area of Science:
- Virology
- Vaccinology
- Nanotechnology
Background:
- Rotaviruses are a leading cause of severe diarrhea in children globally, resulting in significant mortality and economic burden.
- Current rotavirus vaccines, despite their implementation, do not fully prevent disease, necessitating the development of new, highly effective prevention strategies.
Purpose of the Study:
- To evaluate the efficacy of a novel S-VP8* nanoparticle vaccine candidate against rotavirus infection in a mouse model.
- To assess the protective immune response generated by the S-VP8* vaccine against homologous rotavirus challenge.
Main Methods:
- Construction of S-VP8* nanoparticles displaying murine rotavirus (EDIM strain) VP8* antigens (S-mVP8*).
- Immunization of mice with the S-mVP8* vaccine.
- Challenge of immunized mice with the homologous murine EDIM rotavirus and assessment of virus shedding.
Main Results:
- Immunization with S-mVP8* induced high titers of anti-EDIM VP8* IgG antibodies.
- The S-mVP8* nanoparticle vaccine demonstrated high efficacy (97%) in protecting mice against rotavirus challenge, measured by reduced virus shedding.
Conclusions:
- The polyvalent S-VP8* nanoparticle vaccine is a promising candidate for rotavirus prevention.
- Further development of this nanoparticle-based vaccine strategy is warranted based on its high efficacy in a preclinical challenge model.
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.
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