ABSTRACT
This chapter described the studies that evaluated the immunogenicity and protective efficacy of norovirus GII.4 derived P particle and VLP vaccines in comparison to prior norovirus infection and the dose effects of P particles using the Gn pig model. Pigs were orally inoculated once with 10 ID50 live norovirus GII.4/2006b variant or intranasally inoculated with three doses of GII.4/VA387-derived P particles (100 or 250 µg/dose) or VLP (100 µg/dose) with MPL and chitosan adjuvants. Prior HuNoV infection and high dose (250 µg) P particles conferred partial protection from viral shedding (48.6% and 60%). Prior infection, high and low dose P particles, and VLP vaccines conferred partial protection against diarrhea (82.9%, 60%, 46.7%, 60%) compared to the controls following challenge with the GII.4/2006b variant. High dose P particles primed for higher activated T cells, IFN-γ producing T cells, and decreased regulatory T cells post-challenge. Protection rate against diarrhea was positively correlated with expansions of activated CD25+CD4+ and CD25+CD8+ T cells and IFN-γ producing CD4+ and CD8+ T cells in ileum and spleen but was negatively correlated with expansion of CD4+CD25-FoxP3+ regulatory T cells in the duodenum.
