Schedules and protection, simultaneous vaccination and safety: Experiences from recent controlled trials

Abstract

Controlled clinical trials of pertussis vaccines are reviewed, and additional data are presented to elucidate the influence of simultaneous administration of other vaccines on early :symptoms after vaccination and the effect of number of doses, age, and dose-interval on observed efficacy. In a randomized placebo-controlled trial of a two-component acellular diphtheria, tetanus toxoids, pertussis (DTP) vaccine, a five-component acellular DTP, an American whole-cell DTP, and a DT vaccine, adverse events were documented by questionnaires 24 hours after vaccination in 9823 children 2 to 6 months of age. In another ongoing randomized double-blind trial, 82,892 children were enrolled in four DTP groups. An interim analysis of relative efficacy was done when one vaccine was unblinded, due to the low efficacy shown in the first trial. In the placebo-controlled trial, simultaneous administration of Haemophilus influenzae type b (Hib) vaccine increased the rate of systemic symptoms as compared to acellular DTP or DT alone. In the ongoing trial, the relative risk of culture-confirmed pertussis with cough for 1 or more days was 2.82 (2.06–3.88) after two doses of a two-component DTP vaccine compared to a three-component, a five-component, and a British whole-cell DTP vaccine, combined. Simultaneous Hib-vaccination is associated with increased rates of systemic symptoms compared to DT or acellular DTP alone. Two doses of multicomponent acellular vaccines and a British whole-cell vaccine seem to confer significant protection against mild and severe pertussis.