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.