Randomised controlled trial of two-component, three-component, and five-component acellular pertussis vaccines compared with whole-cell pertussis vaccine

Trials in Italy and Sweden showed high efficacy for three-component and five-component pertussis vaccines, and poor efficacy for a whole-cell vaccine licensed in the USA and a two-component vaccine. We compared the efficacy of three acellular vaccines with a UK whole-cell vaccine. We enrolled 82892 babies aged 2–3 months. Babies were vaccinated at age 3 months, 5 months, and 12 months, or age 2 months, 4 months, and 6 months. They were randomly assigned a two-component acellular diphtheria-tetanus-pertussis (DTP) vaccine (n=20697), a three-component acellular DTP vaccine (n=20728), a five-component acellular DTP vaccine (n=20747), or a UK whole-cell DTP vaccine (n=20720). We collected data for all reported cases of culture-confirmed pertussis during 3 years of follow-up. The treatment status of the two-component-vaccine group had to be made known midway through the trial for boosting because of poor efficacy. We included data for the two-component vaccine in the analysis of safety and immunogenicity, and data up its unmasking in secondary analyses of relative efficacy. Analyses were by intention to treat. During follow-up from the third dose (mean 22 months), in the 3 months, 5 months, 12 months schedule, there were 15 cases of culture-confirmed pertussis with at least 21 days of paroxysmal cough in the whole-cell group, relative risk 1·00, compared with 13 in the five-component group (0·85 [95% Cl 0·41–1·79]), and 21 in the three-component group (1·38 [0·71–2·69]). For culture-confirmed pertussis, with or without cough, there were 19 cases in the whole-cell group (1·00), 27 in the five-component group (1·40 [0·78–2·52]), and 49 in the three-component group (2·55 [1·50–4·33]). In the intention-to-treat analyses, from the first dose in the 3 months, 5 months, 12 months schedule the whole-cell vaccine was significantly more protective than the three-component vaccine against typical pertussis. Between the second and the third doses, culture-confirmed pertussis with any cough and with at least 21 days of paroxysmal cough was significantly more frequent in the two-component group than in the three-component group, and in the three-component group than in the five-component and the whole-cell groups, respectively. The serological response of the acellular vaccines in the 2 months, 4 months, 6 months schedule were similar to those previously reported. The whole-cell vaccine was highly immunogenic for fimbriae, pertactin, and filamentous haemagglutinin, but had a