A live quadrivalent rotavirus vaccine containing the serotype 3 rhesus rotavirus vaccine strain and three human x RRV reassortant viruses representing VP7 serotype 1 (D x RRV), 2 (DS1 x RRV) or 4 (ST3 x RRV) was tested in several phase I trials in Venezuelan infants. The vaccine did not produce significant reactions when 4 x 10(4) or 4 x 10(5) PFU were administered in one or two doses. Most of the infants tested developed a seroresponse to at least one of the vaccine components. Approximately one half of the children developed a neutralizing antibody response to human rotavirus serotype 1 or 3 after two doses of the higher titered vaccine whereas a response to serotype 2 or 4 was somewhat less (approximately 40%). Development of neutralizing antibody to each of the four serotypes by 50% or more susceptible vaccinees was set as a goal for quadrivalent vaccines to used in future phase II and phase clinical trials. In studies in Peru, the serotype 3 rhesus rotavirus (RRV) vaccine and two human rotavirus x RRV reassortants of serotype 1 or 2 were evaluated for efficacy as monovalent vaccines in 2 month old infants. Vaccine administration was not associated with fever, diarrhea or respiratory symptoms. A seroresponse was detected in 49-70% of the children by IgA ELISA, but fewer than 20% of the children developed a neutralizing antibody seroresponse to human rotavirus strains. The RRV vaccine induced a low level of protection (30%) over the 2-year follow up period, whereas the serotype 1 (D x RRV) and serotype 2 (DS1 x RRV) reassortant vaccine candidates did not induce protection.
