Amanna IJ, Carlson NE, Slifka MK. N Engl J Med. 2007;357(19):1903–1915

PURPOSE OF THE STUDY. To better define the duration of humoral immunity and the role played by memory B cells.

STUDY POPULATION. There were 45 human subjects followed for up to 26 years. These participants were recruited from the Oregon National Primate Research Center. The only inclusion criteria was that subjects had at least 3 serum samples banked for at least 3 years before the study began. The average age at the start and end of the study was 37 and 52 years, respectively.

METHODS. Blood samples were drawn at least annually, and serum was banked. Antibody titers were measured to vaccinia, measles, mumps, rubella, varicella-zoster, Epstein-Barr, tetanus, and diphtheria. Each subject gave an average of 14 serum samples over an average of 15.2 years. Also, the investigators measured antigen-specific memory B cells by means of limiting-dilution analysis and compared memory B-cell frequencies to their corresponding serum antibody levels. The majority of subjects had vaccination to smallpox in childhood and had recovered from the other viral diseases such as measles and rubella.

RESULTS. The antibody responses to viral antigens were very stable, with estimated half-lives ranging from 50 years for varicella-zoster to >200 years for measles and mumps. Against tetanus and diphtheria, the antibody responses waned more rapidly with half-lives of 11 and 19 years, respectively. The investigators also found that B-cell memory was long-lived, but there was no significant correlation between peripheral memory B-cell numbers and antibody levels for 5 of the 8 antigens.

CONCLUSIONS. Serologic memory for multiple antigens is maintained for remarkably sustained periods of time. Also, memory B-cell numbers did not correlate with antibody titers, which 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 immunity.

REVIEWER COMMENTS. At the end of the study, the average age of the participants was 52 years. Most had received vaccination to smallpox, but most had also contracted natural measles, mumps, or rubella during childhood. This study population, therefore, does not represent our current population of children with complex schedules of vaccinations. Furthermore, we cannot conclude from this study that vaccination-induced immunity is necessarily as long-lived as natural infection-induced immunity. Nonetheless, this report does give fascinating insight into the “adult” side of immunity to many of the childhood diseases against which we vaccinate. This study also sheds light on possible mechanisms for sustained humoral immunity, which it seems may not entirely depend on regulation by memory B cells.

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