Duration of humoral immunity to common viral and vaccine antigens

N Engl J Med. 2007 Nov 8;357(19):1903-15. doi: 10.1056/NEJMoa066092.


Background: Maintenance of long-term antibody responses is critical for protective immunity against many pathogens. However, the duration of humoral immunity and the role played by memory B cells remain poorly defined.

Methods: We performed a longitudinal analysis of antibody titers specific for viral antigens (vaccinia, measles, mumps, rubella, varicella-zoster virus, and Epstein-Barr virus) and nonreplicating antigens (tetanus and diphtheria) in 45 subjects for a period of up to 26 years. In addition, we measured antigen-specific memory B cells by means of limiting-dilution analysis, and we compared memory B-cell frequencies to their corresponding serum antibody levels.

Results: Antiviral antibody responses were remarkably stable, with half-lives ranging from an estimated 50 years for varicella-zoster virus to more than 200 years for other viruses such as measles and mumps. Antibody responses against tetanus and diphtheria antigens waned more quickly, with estimated half-lives of 11 years and 19 years, respectively. B-cell memory was long-lived, but there was no significant correlation between peripheral memory B-cell numbers and antibody levels for five of the eight antigens tested.

Conclusions: These studies provide quantitative analysis of serologic memory for multiple antigens in subjects followed longitudinally over the course of more than one decade. In cases in which multiple exposures or repeated vaccinations were common, memory B-cell numbers did not correlate with antibody titers. This finding suggests that peripheral memory B cells and antibody-secreting plasma cells may represent independently regulated cell populations and may play different roles in the maintenance of protective immunity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aging / immunology
  • Antibodies, Bacterial / blood*
  • Antibodies, Viral / blood*
  • Antibody Formation*
  • Antigens, Bacterial / immunology*
  • Antigens, Viral / immunology*
  • B-Lymphocytes*
  • Diphtheria / immunology
  • Female
  • Half-Life
  • Humans
  • Longitudinal Studies
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Plasma Cells / immunology
  • Seroepidemiologic Studies
  • Tetanus / immunology
  • Time Factors
  • Vaccines / immunology*
  • Virus Diseases / immunology


  • Antibodies, Bacterial
  • Antibodies, Viral
  • Antigens, Bacterial
  • Antigens, Viral
  • Vaccines