ObjectiveTo compare the safety and immunogenicity of two dosages of tetravalent rhesus rotavirus vaccine (RRV-TV) and the effect of age at dosing.MethodsA total of 195 infants were stratified by age into 2 groups, 6 to 12 weeks and 16 to 24 weeks, and randomly assigned to receive a single dose of placebo or RRV-TV containing either 4 × 105or 4 × 106plaque-forming units (pfu). Symptoms were recorded for 5 days after vaccination. Anti-rotavirus IgA and neutralizing antibody to human rotavirus serotypes G1 to G4 and RRV were measured in serum obtained pre- and post-vaccination.ResultsRates of fever >38°C (9%), diarrhea (6%) and vomiting (8%) were similar in all groups. IgA (69%vs. 49%,P= 0.02) and RRV (85%vs. 66%,P= 0.004) seroconversion rates were significantly higher in the 4 × 106pfu vaccine group as were antibody titers to RRV (440.2vs. 263.7,P= 0.04). Older infants demonstrated significantly higher seroconversion rates and antibody titers for IgA (71%vs. 52%,P= 0.03; and 110.6vs. 54.8,P= 0.004) and RRV (92%vs. 66%,P= 0.05 and 498.3vs. 205.6,P= 0.01) at either dose level than did the younger infants. There were no significant differences in seroconversion rates or antibody titers to human rotavirus types G1 to G4 between the two vaccination groups.ConclusionsRRV-TV at a dose of 4 × 106pfu can be safely administered to infants 6 to 24 weeks of age. A single dose of 4 × 106pfu of RRV-TV was significantly more immunogenic than a single dose of 4 × 105pfu but did not improve responses to the human serotypes. Older vaccine recipients demonstrated significantly higher IgA and neutralizing antibody seroconversion rates and antibody titers than younger infants independent of dosage.