ABSTRACT
This chapter discussed two subunit rotavirus vaccines. Rotavirus outer capsid spike protein VP4, in the presence of trypsin, is cleaved to produce VP8* and VP5*. ∆VP8* subunit protein containing amino acid residues 64 (or 65)-223 with P[8], P[4] or P[6] specificity elicited high levels of homotypic and varying levels of heterotypic virus-neutralizing antibodies in small animals immunized intramuscularly, thus demonstrating a solid vaccine potential. The P2-P[8]VP8* and P2-P[6]VP8* constructs were expressed in Escherichia coli and the immunogenicity and protective efficacy of these recombinant fusion proteins were characterized in guinea pigs and Gn pigs. The encouraging protective efficacy demonstrated in Gn pigs led to further development of the P2-VP8* vaccine by PATH for optimized formulations in the presence of aluminum adjuvants. The norovirus P particle, referred to as the P24 particle, is an octahedral nanoparticle composed of 24 copies of the protrusion (P) domain of the norovirus capsid protein. The P24-VP8* nanoparticle consists of a 24-valent core of P particle and 24 surface-displayed VP8*. The immunogenicity and protective efficacy of this P24-VP8* nanoparticle vaccine were evaluated in the Gn pig model and it was shown to be immunogenic and highly effective in reducing virus shedding and diarrhea.
