Durability of Vaccine-Induced Immunity Against Tetanus and Diphtheria Toxins: A Cross-sectional Analysis

Abstract

Background: Many adult immunization schedules recommend that tetanus and diphtheria vaccination be performed every 10 years. In light of current epidemiological trends of disease incidence and rates of vaccine-associated adverse events, the 10-year revaccination schedule has come into question.

Methods: We performed cross-sectional analysis of serum antibody titers in 546 adult subjects stratified by age or sex. All serological results were converted to international units after calibration with international serum standards.

Results: Approximately 97% of the population was seropositive to tetanus and diphtheria as defined by a protective serum antibody titer of ≥0.01 IU/mL. Mean antibody titers were 3.6 and 0.35 IU/mL against tetanus and diphtheria, respectively. Antibody responses to tetanus declined with an estimated half-life of 14 years (95% confidence interval, 11-17 years), whereas antibody responses to diphtheria were more long-lived and declined with an estimated half-life of 27 years (18-51 years). Mathematical models combining antibody magnitude and duration predict that 95% of the population will remain protected against tetanus and diphtheria for ≥30 years without requiring further booster vaccination.

Conclusions: These studies demonstrate that durable levels of protective antitoxin immunity exist in the majority of vaccinated individuals. Together, this suggests that it may no longer be necessary to administer booster vaccinations every 10 years and that the current adult vaccination schedule for tetanus and diphtheria should be revisited.

Keywords: cross-sectional analysis; diphtheria; immunological memory; tetanus.

Figure 1.

Humoral immunity to tetanus as a function of age and time after vaccination. Tetanus-specific serum antibody responses were measured in adult subjects and plotted versus age (A) or time after vaccination (B). Dotted line in each panel represents level of antibody required for protection, equivalent to 0.01 IU/mL. B, Solid blue line is the fitted regression line representing the antibody half-life decay rate, and the shaded blue region represents the upper and lower bound of 95% confidence interval (CI) for the cross-sectional antibody half-life estimation. Dashed blue line represents a 1-sided lower bound 95% CI based on a 14-year half-life and indicates when tetanus-specific antibody titers would decline to 95% seroprotection by crossing the protective threshold of 0.01 IU/mL (ie, −2 log₁₀ IU/mL) at 72 years after vaccination. Dashed green line is based on an estimated 11-year half-life [7] and indicates that 95% of the population will remain protected against tetanus for 64 years after vaccination.

Figure 2.

Humoral immunity to diphtheria as a function of age and time after vaccination. Diphtheria-specific serum antibody responses were measured in adult subjects and plotted versus age (A) or time after vaccination (B). Dotted line in each panel represents level of antibody required for protection, equivalent to 0.01 IU/mL. B, Solid blue line is the fitted regression line representing the antibody half-life decay rate, and the shaded blue region represents the upper and lower bound of 95% confidence interval (CI) for the antibody half-life estimation. Dashed blue line represents a 1-sided lower bound 95% CI based on a 27-year half-life and indicates when diphtheria-specific antibody titers would decline to 95% seroprotection by crossing the protective threshold of 0.01 IU/mL (ie, −2 log₁₀ IU/mL) at 42 years after vaccination. Dashed green line is based on an estimated 19-year half-life [7] and indicates that 95% of the population will remain protected against diphtheria for 30 years after vaccination.