A dual vaccine candidate against norovirus and hepatitis E virus

Norovirus (NoV) and hepatitis E virus (HEV) are both enterically-transmitted viruses causing gastroenteritis and hepatitis, respectively, in humans. While a vaccine against HEVs recently became available in China, there is no prophylactic or therapeutic approach against NoVs. Both NoV and HEV have surface protrusions formed by dimers of the protruding (P) domains of the viral capsids, which is responsible for virus-host interactions and eliciting viral neutralizing antibody. We developed in this study a bivalent vaccine against the two viruses through a recently developed polyvalent complex platform. The dimeric P domains of NoV and HEV were fused together, designated as NoV P(-)-HEV P, which was then linked with the dimeric glutathione-S-transferase (GST). After expression and purification in E. coli, the GST-NoV P(-)-HEV P fusion protein assembled into polyvalent complexes with a mean size of 1.8μm, while the NoV P(-)-HEV P formed oligomers ranging from 100 to 420kDa. Mouse immunization study demonstrated that both GST-NoV P(-)-HEV P and NoV P(-)-HEV P complexes induced significantly higher antibody titers to NoV P(-) and HEV P, respectively, than those induced by a mixture of the NoV P(-) and HEV P dimers. Furthermore, the complex-induced antisera exhibited significantly higher neutralizing activity against HEV infection in HepG2/3A cells and higher blocking activity on NoV P particles binding to HBGA receptors than those of the dimer-induced antisera. Thus, GST-NoV P(-)-HEV P and NoV P(-)-HEV P complexes are promising dual vaccine candidates against both NoV and HEV.