Reduced Antibody Response to Infant Measles Vaccination: Effects Based on Type and Timing of the First Vaccine Dose Persist After the Second Dose.

BACKGROUND

The effect of age at first dose on the immunogenicity of a 2-dose pediatric schedule of measles-mumps-rubella (MMR) or measles-mumps-rubella-varicella (MMRV) vaccine was assessed in children born to mostly vaccinated mothers.

METHODS

Immunogenicity data among children given their first measles vaccine dose between 11 and 22 months of age were pooled from 5 randomized controlled trials conducted in Europe and the United States between 2004 and 2010. Measles antibody titers were measured by enzyme-linked immunosorbent assay before and after each dose; geometric mean concentrations (GMCs) and the proportion seronegative (GMC <150 mIU/mL) were derived by age at first dose.

RESULTS

Among 5542 children given a first measles vaccine dose at 11, 12, 13-14, and 15-22 months of age, the proportion seronegative decreased from 8.5% to 3.2%, 2.4%, and 1.5%, respectively (P < .001), whereas GMCs increased with older age measles vaccine initiation (P < .001). MMRV induced higher GMCs than MMR (P < .001). First and second dose GMCs were highly correlated (Spearman coefficient = 0.8).

CONCLUSIONS

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 vs ≥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 <15 months of age.