Acellular pertussis vaccines effectiveness over time: A systematic review, meta-analysis and modeling study

Abstract

Background: Acellular pertussis vaccine studies postulate that waning protection, particularly after the adolescent booster, is a major contributor to the increasing US pertussis incidence. However, these studies reported relative (ie, vs a population given prior doses of pertussis vaccine), not absolute (ie, vs a pertussis vaccine naïve population) efficacy following the adolescent booster. We aim to estimate the absolute protection offered by acellular pertussis vaccines.

Methods: We conducted a systematic review of acellular pertussis vaccine effectiveness (VE) publications. Studies had to comply with the US schedule, evaluate clinical outcomes, and report VE over discrete time points. VE after the 5-dose childhood series and after the adolescent sixth-dose booster were extracted separately and pooled. All relative VE estimates were transformed to absolute estimates. VE waning was estimated using meta-regression modeling.

Findings: Three studies reported VE after the childhood series and four after the adolescent booster. All booster studies reported relative VE (vs acellular pertussis vaccine-primed population). We estimate initial childhood series absolute VE is 91% (95% CI: 87% to 95%) and declines at 9.6% annually. Initial relative VE after adolescent boosting is 70% (95% CI: 54% to 86%) and declines at 45.3% annually. Initial absolute VE after adolescent boosting is 85% (95% CI: 84% to 86%) and declines at 11.7% (95% CI: 11.1% to 12.3%) annually.

Interpretation: Acellular pertussis vaccine efficacy is initially high and wanes over time. Observational VE studies of boosting failed to recognize that they were measuring relative, not absolute, VE and the absolute VE in the boosted population is better than appreciated.

Fig 1. Meta-analysis of acellular pertussis vaccines.

This figure represents the relative risk (OR) of pertussis infection occurring at different time points after vaccination. The I2 values (i.e. Higgin’s I2) quantifies the proportion of heterogeneity and dispersion in the meta-analytic model. Panel A: Represents a Meta-analysis of the OR of pertussis infection when comparing children immunized with the primary acellular pertussis series (5-dose DTaP) compared to vaccine naïve children. These OR values in Panel A were the product of a mathematical transformation of relative (5-dose DTaP) OR values. Panel B: Represents a meta-analysis of the OR of pertussis infection when comparing children immunized with the full acellular pertussis series (5-dose DTaP and 1-dose Tdap) compared to children immunized with only the primary acellular pertussis series.

Fig 2. Acellular pertussis vaccine effectiveness (VE) over time.

Panel A: The blue line represents the absolute VE (ie, vs a pertussis vaccine naïve population) of the 5-dose DTaP childhood series. The grey line represents the relative VE (ie, vs DTaP vaccine-primed population) of 1-dose Tdap vaccine given in early adolescence, as reported by previous researchers. Panel B: The blue line again represents the absolute VE of the primary acellular pertussis series. The red line represents the modeled absolute VE of the full acellular pertussis series (ie, 1 dose of Tdap vaccine given in early adolescence 6 years after completion of the DTaP childhood series).