Jennerian reassortment rotavirus vaccines

Kim, Kyoung Hee

Abstract

RQtavirus(Rv) is the most common cause of severe dehydratine diarrhea in infants and young children worldwide, infecting nearly every child in the first few years of life, and thus justif}-ing universal childhood immunization when a safe and effective vaccine is available. In Korea, Rv is the most pi evalent enteropathogen identified in the stools of children with diarrhea, accounting for 46 to 68% of cases. Rv contains 11 segments of double-stranded RNA, each coding for a viral protein, inside a 70-nm triple layered protein capsid. Of particular interest for vaccine development are the two outer capsid proteins, VP7 and VP4, that are involved in viral virulence, host range restriction, hemagglutination, serotype specificity, neutralization, disease prevention, and cell attachment and penetration. The two neutralization proteins form the basis for the current classfication of group A Rv into G(VP7) and P(VP4) serotypes. To date at least 9 human G serotypes and 6 human P serotypes have been found, with GI through G4, P4 and P8 being the most prevalent. For most countries surveyed, including Korea, four main types are G1P8, G2P4, G3P8, and G4P8. In India, however, P6(G1P6, G2P6, G3P6, G4P6, and G9P6) that primarily infect asymptomatic newborns but are rare in diarrheal children were common with G9P6, a strain not previously reported in diarrhea( children, the most prevalent. Rv crosses species barriers. The rhesus monkey Rv strain MMU18006(RRV, G3) was found to be immunogenic and mildly reactogenic human trials. The RRV vaccine was protective against homotypic G3 illness, but efficacy against heterotypic Rv strains was variable. Since Rv has a segmented genome, one approach that has been taken to induce protection against human serotypes is to use a monovalent vaccine(RRV-GI) containing a human Rv with Gl VP7 and 10 RRV genes because G1 infections are the most common. Another approach is to use the tetravalent vaccine (RRV-TV) containing 4 viruses including one each in which the VP7 for human GI, 2, or 4 replaced the RRV VP7, as well as RRV itself, which has a VP7 corresponding to G3. In randomized, double-blind trials in the US, both live oral RRV-G1 and RRV-TV, reduced the incidence of Rv gastroenteritis (P < 0.001). Vaccine efficacy against disease caused by GI infection, the most common type detected in the US (7190, was 44% for RRV-TV and 5 5 % for RRV-S 1. RRV-TV and RRV-S1 prevented 77% and 45%, respectively, of disease caused by G3, the second most common type (1991)) in the US at the time of the study. Current Jennerian reassortant vaccines that contain only VP7 antigens from human strains could be improved by addition of a VP4 gene from a human strain as a separate reassorrant.