title: Randomised controlled trial of two-component, three-component, and five-component acellular pertussis vaccines compared with whole-cell pertussis vaccine. Ad Hoc Group for the Study of Pertussis Vaccines.
abstract: BACKGROUND
  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.
  
  
  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 months, 4 months, and 6 months. They were randomly assigned a two-component acellular diphtheria-tetanus-pertussis (DTP) vaccine (n = 20,697), a three-component acellular DTP vaccine (n = 20,728), a five-component acellular DTP vaccine (n = 20,747), or a UK whole-cell DTP vaccine (n = 20,720). 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.
  
  
  RESULTS
  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% CI 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 low antipertussis toxin response. Hypotonic hyporesponsiveness 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 whole-cell vaccine than after any of the acellular vaccines (p < 0.001).
  
  
  CONCLUSIONS
  The efficacy of the UK whole-cell vaccine and the five-component and three-component vaccines was similar against culture-confirmed pertussis with at least 21 days of paroxysmal cough. The lower efficacy of the three-component vaccine against mild disease suggests that fimbriae have a role in protection against infection. The efficacy of acellular vaccines depends on the number of components, and different whole-cell vaccines have variable efficacies.
authors.affiliation: Swedish Institute for Infectious Disease Control, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Olin
authors.forename: F
authors.initials: F
authors.lastname: Rasmussen
authors.forename: L
authors.initials: L
authors.lastname: Gustafsson
authors.forename: H O
authors.initials: HO
authors.lastname: Hallander
authors.forename: H
authors.initials: H
authors.lastname: Heijbel
mesh_terms: D000917:Antibody Formation; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007223:Infant; D008297:Male; D010567:Pertussis Vaccine / Q000008:administration & dosage* / Q000009:adverse effects*; D014917:Whooping Cough / Q000276:immunology* / Q000517:prevention & control
chemical_list: D015721:Diphtheria-Tetanus-Pertussis Vaccine; D007074:Immunoglobulin G; D010567:Pertussis Vaccine