The effect of age at first dose on the immunogenicity of a two-dose pediatric schedule of Measles-Mumps-Rubella (MMR) or MMR-Varicella (MMRV) vaccines was assessed in children born to mostly vaccinated mothers. Immunogenicity data among children given their first measles vaccine dose between 11 and 22 months of age were pooled from five randomized controlled trials conducted in Europe and the United States between 2004 and 2010. Measles antibody titers were measured by ELISA before/after each dose: geometric mean concentrations (GMCs) and the proportion sero-negative (GMC<150mIU/ml) were derived by age at first dose. Among 5542 children given a first measles vaccine dose at 11, 12, 13-14 and 15-22 months of age, the proportion sero-negative decreased from 8.5% to 3.2%, 2.4% and 1.5%, respectively (p<0.001), whereas GMCs increased with older age measles vaccine initiation (p<0.001). First and second dose GMCs were highly correlated (Spearman coefficient=0.8) and MMRV induced higher GMCs than MMR (p<0.001). As previously noted among infants born to mothers with history of wild-type measles, antibody responses among children born to vaccinated mothers were reduced based on earlier administration of their first measles vaccine dose at ≤12 versus ≥15 months of age. Negative effects of earlier age at first measles vaccine dose persisted after the second dose. The measles elimination goal may require a careful balance between earlier infant protection and the risk of reduced antibody responses and secondary vaccine failure among successive birth cohorts systematically initiated to measles vaccination below 15 months of age.
