Development of a pentavalent rotavirus vaccine against prevalent serotypes of rotavirus gastroenteritis.

The strategy of decreasing the morbidity and mortality associated with rotavirus gastroenteritis through vaccination is supported by studies demonstrating that wild-type rotavirus infection protects against subsequent rotavirus disease. Primary infection with wild-type rotavirus typically induces homotypic immunity. Vaccination of infants with a multivalent vaccine directed against prevalent rotavirus serotypes is the strategy most likely to provide the broadest degree of protection against rotavirus gastroenteritis. The pentavalent human-bovine reassortant rotavirus vaccine (HBRV) is directed against each of the most prevalent rotavirus serotypes, including G1, G2, G3, G4, and P1. The safety, immunogenicity, and efficacy of different reassortant compositions and formulations of the HBRV have been evaluated in clinical trials. An HBRV dose of > or =8 x 10(6) plaque-forming units has demonstrated 68.8%-76.6% efficacy against any rotavirus gastroenteritis, regardless of severity, and approximatel 100% efficacy against severe rotavirus gastroenteritis for the first rotavirus infection season after vaccination. The HBRV has been generally well tolerated, with no increase in the incidence of fever, vomiting, diarrhea, or behavioral changes among vaccine recipients, compared with placebo recipients, during the 14- and 42-day periods after administration of any dose. Shedding of vaccine strains in feces is uncommon. A large-scale trial is under way to evaluate the efficacy and safety of the manufacturing-scale formulation of pentavalent HBRV.