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

Clin Infect Dis. 2017 Oct 1;65(7):1094-1102. doi: 10.1093/cid/cix510.


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.

Publication types

  • Meta-Analysis
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral
  • Antibody Formation / immunology*
  • Chickenpox / immunology
  • Chickenpox Vaccine / immunology
  • Europe
  • Female
  • Herpesvirus 3, Human / immunology
  • Humans
  • Immunization Schedule
  • Immunization, Secondary / methods
  • Infant
  • Male
  • Measles / immunology*
  • Measles Vaccine / immunology*
  • Measles virus / immunology
  • Measles-Mumps-Rubella Vaccine / immunology
  • Mumps / immunology
  • Randomized Controlled Trials as Topic
  • Rubella / immunology
  • Rubella virus / immunology
  • Vaccination / methods
  • Vaccines, Combined / immunology


  • Antibodies, Viral
  • Chickenpox Vaccine
  • Measles Vaccine
  • Measles-Mumps-Rubella Vaccine
  • Vaccines, Combined
  • measles, mumps, rubella, varicella vaccine