RANDOMIZED CONTROLLED TRIAL OF 2-COMPONENT, 3-COMPONENT, AND 5-COMPONENT ACELLULAR PERTUSSIS VACCINES COMPARED WITH WHOLE-CELL PERTUSSIS-VACCINE

Background Trials in Italy and Sweden showed high efficacy for three-c omponent 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-c ell vaccine. Methods We enrolled 82 892 babies aged 2-3 months. Babies were vaccinated at age 3 months, 5 months, and 12 months, or age 2 mo nths, 4 months, and 6 months. They were randomly assigned a two-compon ent acellular diphtheria-tetanus-pertussis (DTP) vaccine (n=20 697), a three-component acellular DTP vaccine (n=20 728), a five-component ac ellular DTP vaccine (n=20 747), or a UK whole-cell DTP vaccine (n=20 7 20). We collected data for all reported cases of culture-confirmed per tussis during 3 years of follow-up. The treatment status of the two-co mponent-vaccine group had to be made known midway through the trial fo r boosting because of poor efficacy. We included data for the two-comp onent vaccine in the analysis of safety and immunogenicity, and data u p its unmasking in secondary analyses of relative efficacy. Analyses w ere by intention to treat. Findings During follow-up from the third do se (mean 22 months), in the 3 months, 5 months, 12 months schedule, th ere were 15 cases of culture-confirmed pertussis with at least 21 days of paroxysmal cough in the whole-cell group, relative risk 1.00, comp ared with 13 in the five-component group (0.85 [95% CI 0.41-1.79]), an d 21 in the three-component group (1.38 [0.71-2.69]). For culture-conf irmed pertussis, with or without cough, there were 19 cases in the who le-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 inte ntion-to-treat analyses, from the first dose in the 3 months, 5 months , 12 months schedule the whole-cell vaccine was significantly more pro tective than the three-component vaccine against typical pertussis. Be tween the second and the third doses, culture-confirmed pertussis with any cough and with at least 21 days of paroxysmal cough was significa ntly more frequent in the two-component group than in the three-compon ent 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 we re similar to those previously reported, The whole-cell vaccine was hi ghly immunogenic for fimbriae, pertactin, and filamentous haemagglutin in, but had a low antipertussis toxin response. Hypotonic hyporesponsi veness occurred significantly more frequently in the whole-cell group (p<0.05) and was more frequent in the acellular groups than previously reported. High fever and seizures occurred more frequently after whol e-cell vaccine than after any of the acellular vaccines (p<0.001). Int erpretations The efficacy of the UK whole-cell vaccine and the five-co mponent and three-component vaccines was similar against culture-confi rmed pertussis with at least 21 days of paroxysmal cough. The lower ef ficacy of the three-component vaccine against mild disease suggests th at fimbriae have a role in protection against infection. The efficacy of acellular vaccines depends on the number of components, and differe nt whole-cell vaccines have variable efficacies.