title: Tetravalent human-rhesus reassortant rotavirus vaccine: a review of its immunogenicity, tolerability and protective efficacy against paediatric rotavirus gastroenteritis.
abstract: Tetravalent human-rhesus reassortant rotavirus vaccine (RRV-TV) contains the rhesus rotavirus (RRV) strain MMU 18006, which has serotype G3 specificity, and reassortant rotavirus strains with human serotype G1, G2 and G4 specificity. Rotavirus gastroenteritis in humans is predominantly caused by these 4 serotypes. RRV-TV 4 x 10(4), 4 x 10(5) or 4 x 10(6) plaque-forming units (PFU) per dose induces seroresponse rates (generally defined as a >or=4-fold increase in antibody titre) of 48 to 93% for IgA against RRV and 49 to 90% for neutralising antibodies to RRV after 1 to 3 doses in infants aged >or=4 weeks. Seroresponse rates for neutralising antibodies to human serotypes G1, G2, G3 and G4 are generally lower (2 to 68%). The rates generally increase with sequential doses, but not necessarily with increased vaccine titre. Seroresponse rates appear to be better in older infants than in neonates or infants aged <or=12 weeks. RRV-TV is more immunogenic against human G2, G3 and G4 serotypes than the monovalent serotype G1 human-rhesus reassortant rotavirus vaccine (RRV-S1) and tends to be more immunogenic against G1, G2 and G3 serotypes than the human serotype G1 strain vaccine M37. In most settings, RRV-TV has at least moderate efficacy in reducing the incidence of rotavirus gastroenteritis. Importantly, it protects against severe disease, with efficacy rates of 69 to 100% against very severe rotavirus gastroenteritis in large scale studies in the US, Finland and Venezuela. RRV-TV has similar overall efficacy to RRV-S1, but provides greater protection against gastroenteritis caused by rotavirus strains of serotypes other than G1. The efficacy of RRV-TV is not significantly affected by breast feeding or concurrent use of oral poliovirus vaccine. The only adverse effect with which RRV-TV has been associated is a mild, transient febrile reaction. Limited data from the US and Finland suggest that vaccination with RRV-TV could be cost saving. In conclusion, the incidence of paediatric rotavirus gastroenteritis, particularly severe cases, would be reduced in most settings by the incorporation of RRV-TV into routine childhood immunisation schedules. Further refinements to RRV-TV (and/or development of additional candidate vaccines) may eventually produce even greater protective efficacy. In the meantime, RRV-TV is a significant advance in the prevention of paediatric rotavirus gastroenteritis worldwide.
authors.affiliation: Adis International Limited, Auckland, New Zealand. demail@adis.co.nz
authors.forename: R H
authors.initials: RH
authors.lastname: Foster
authors.forename: A J
authors.initials: AJ
authors.lastname: Wagstaff