ABSTRACT
Simvastatin is a cholesterol-reducing drug that is known to increase human norovirus (HuNoV) infectivity. In this chapter, simvastatin’s effects on norovirus P particle vaccine-induced protective efficacy and T cell immunogenicity in the Gn pig model of HuNoV infection and diarrhea were described. Pigs were intranasally inoculated with three doses (100 µg/dose) of HuNoV P particles together with monophosphoryl lipid A and chitosan adjuvants. Simvastatin-fed pigs received 8 mg/day orally for 11 days prior to challenge. A subset of pigs was orally challenged with HuNoV GII.4/2006b variant at post-inoculation day (PID) 28. Simvastatin abolished the P particle vaccine’s protection and significantly increased diarrhea severity after HuNoV infection. Simvastatin decreased proliferation of virus-specific and non-specific CD8 T cells in the duodenum and virus-specific CD4 and CD8 T cells in the spleen and significantly reduced numbers of intestinal mononuclear cells in vaccinated pigs. Furthermore, simvastatin significantly decreased numbers of duodenal CD4+IFN-γ+, CD8+IFN-γ+, and regulatory T cells and total duodenal activated CD4+ and CD8+ T cells in vaccinated pigs at PID 28. Following challenge, simvastatin prevented the IFN-γ+ T cell response in the spleen of vaccinated pigs. The findings have specific implications for vaccination strategy against HuNoV in the elderly population who takes statin-type drugs.
