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Objective: To determine the effect of maternal antibody on hepatitis A vaccine immunogenicity in infants. Study design Infants of mothers negative for antibody to hepatitis A virus (anti-HAV; group 1) were administered hepatitis A vaccine at 2, 4, and 6 months of age, and infants of anti-HAV-positive mothers were randomized to receive either hepatitis A vaccine (group 2) or hepatitis B vaccine (group 3) on the same schedule. Group 3 infants subsequently received hepatitis A vaccine at 8 and 10 months of age., Results: At 15 months of age, 100% of infants in group 1, 93% in group 2, and 92% in group 3 had protective levels of antibody. However, there were significant differences in the geometric mean concentration (GMC) of anti-HAV between groups. Group 1 GMC was 231 mIU/mL, compared with 85 mIU/mL for group 2 and 84 mIU/mL for group 3 (P<.001, group 1 vs group 3)., Conclusions: Passively acquired maternal anti-HAV resulted in a significantly lower final antibody response when infants were administered hepatitis A vaccine at 2, 4, and 6 months of age or at 8 and 10 months of age.