Duration of Immunity to Common Viral andVaccine Antigens

Abstract & Commentary

By Mary Elina Ferris, MD, Clinical Associate Professor, University of Southern California. Dr. Ferris reports no financial relationship to this field of study.

Synopsis: Serum analysis of 45 subjects for antibodies and humoral immunity over a median of 15 years showed antiviral responses ranging from 11-19 years for tetanus-diphtheria, 50 years for varicella-zoster, and up to 200 years for measles and mumps.

Source: Amanna IJ, et al. N Engl J Med. 2007;357:1903-1915.

A mathematical model was used to calcu-late antibody half-life and rates of decay using 630 serum samples collected from 45 individuals over a median of 15.2 years (range 5 to 26 years), with an average of 14 samples per subject. Samples were collected as part of annual screening of laboratory workers with additional samples after any injury; a smaller group had weekly samples after vaccinations.

Antibody titers were measured for 6 viral antigens (vaccinia, measles, mumps, rubella, varicella-zoster virus, and Epstein-Barr virus) and 2 nonreplicating antigens (tetanus and diphtheria). Elevations of antibody levels were seen after booster vaccinations, and the natural decline of antibodies were identical for persons exposed though actual disease vs vaccination, although the absolute level was higher for actual disease exposure.

Varicella-zoster viral immunity showed the most fluctuations. All 45 study subjects were initially seropositive, and the majority of 10 who experienced spikes in antibody level had no known exposures or viral outbreaks. Immunity decreased slowly, with an estimated half-life of 50 years. Tetanus-specific antibodies decreased the most rapidly, with estimated half-life of 11 years; diphtheria-specific antibodies had an estimated half-life of 19 years.

Memory B cells for the 8 specific antigens were also measured with limiting-dilution analysis, and their frequencies compared to corresponding serum antibody levels. B cell levels rose quickly after antigen exposures and persisted. A significant correlation to antibody levels was found after acute infection with measles, mumps, and rubella, but not vaccinia, varicella-zoster or Epstein-Barr viruses, or for the tetanus-diphtheria vaccine antigens.

To test the theory of "nonspecific bystander activation" of humoral immunity being triggered by unrelated infections, 4 subjects were followed for over 25 years for their antibody response to the 8 antigens after unrelated infection or immunization. Little or no effect on antibody levels to these antigens was seen.

Commentary

This longitudinal research both supports and refutes some current theories of how longstanding immunity is maintained. For measles, mumps and rubella, antibody responses were correlated with rises in memory B cells after antigen exposure, which supports the theory that B cell activation into plasma cells is necessary for antibody maintenance. However this association was not present for the other viruses and tetanus-diphtheria antigens, although levels of immunity for both antibodies and B cells were independently maintained.

The authors suggest that a model of independent regulation of antibody levels and memory B cells is the most likely, with multiple re-exposures affecting the levels in different ways. They also note that the shorter duration of antibody levels to the protein antigens for tetanus-diphtheria immunization suggests that antibody maintenance is influenced by the nature of the antigen.

Although this research is an important contribution to the knowledge needed for vaccine design and timing of booster vaccinations, it is not enough to change clinical practice at this point. However, it does appear that our current schedule for immunizations and boosters was sufficient to maintain immunity to these common antigens over a long period of time, even if we're still not exactly sure how it all works.