Measles Virus Neutralizing Antibody Response, Cell-Mediated Immunity, and Immunoglobulin G Antibody Avidity Before and After Receipt of a Third Dose of Measles, Mumps, and Rubella Vaccine in Young Adults

J Infect Dis. 2016 Apr 1;213(7):1115-23. doi: 10.1093/infdis/jiv555. Epub 2015 Nov 23.


Background: Two doses of measles, mumps, and rubella (MMR) vaccine are 97% effective against measles, but waning antibody immunity to measles and failure of the 2-dose vaccine occur. We administered a third MMR dose (MMR3) to young adults and assessed immunogenicity over 1 year.

Methods: Measles virus (MeV) neutralizing antibody concentrations, cell-mediated immunity (CMI), and immunoglobulin G (IgG) antibody avidity were assessed at baseline and 1 month and 1 year after MMR3 receipt.

Results: Of 662 subjects at baseline, 1 (0.2%) was seronegative for MeV-neutralizing antibodies (level, <8 mIU/mL), and 23 (3.5%) had low antibody levels (8-120 mIU/mL). One month after MMR3 receipt, 1 subject (0.2%) was seronegative, and 6 (0.9%) had low neutralizing antibodies, with only 21 of 662 (3.2%) showing a ≥ 4-fold rise in neutralizing antibodies. One year after MMR3 receipt, no subject was seronegative, and 10 of 617 (1.6%) had low neutralizing antibody levels. CMI analyses showed low levels of spot-forming cells after stimulation, suggesting the presence of T-cell memory, but the response was minimal after MMR3 receipt. MeV IgG avidity did not correlate with findings of neutralization analyses.

Conclusions: Most subjects were seropositive before MMR3 receipt, and very few had a secondary immune response after MMR3 receipt. Similarly, CMI and avidity analyses showed minimal qualitative improvements in immune response after MMR3 receipt. We did not find compelling data to support a routine third dose of MMR vaccine.

Keywords: cell-mediated immunity; immunization; measles; measles vaccine immunogenicity; measles virus antibody avidity; third dose of measles, mumps, rubella (MMR) vaccine; vaccine-preventable disease.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Neutralizing / blood*
  • Antibodies, Viral / blood*
  • Antibody Affinity
  • Cohort Studies
  • Female
  • Humans
  • Immunity, Cellular / physiology*
  • Immunization Schedule
  • Immunoglobulin G / blood*
  • Longitudinal Studies
  • Male
  • Measles virus / immunology*
  • Measles-Mumps-Rubella Vaccine / administration & dosage
  • Measles-Mumps-Rubella Vaccine / immunology*
  • Neutralization Tests
  • Odds Ratio
  • Young Adult


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Immunoglobulin G
  • Measles-Mumps-Rubella Vaccine