A controlled trial of two acellular vaccines and one whole-cell vaccine against pertussis. Progetto Pertosse Working Group

N Engl J Med. 1996 Feb 8;334(6):341-8. doi: 10.1056/NEJM199602083340601.

Abstract

Background: Concern about both safety and efficacy has made the use of whole-cell pertussis vaccines controversial. In some European countries, including Italy, the rate of vaccination against pertussis is low.

Methods: We conducted a double-blind trial in Italy in which infants were randomly assigned to vaccination at two, four, and six months of age with an acellular pertussis vaccine together with diphtheria and tetanus toxoids (DTP); a DTP vaccine containing whole-cell pertussis (manufactured by Connaught Laboratories); or diphtheria and tetanus toxoids without pertussis (DT). The acellular DTP vaccine was either one containing filamentous hemagglutinin, pertactin, and pertussis toxin inactivated with formalin and glutaraldehyde (SmithKline Beecham) or one with filamentous hemagglutinin, pertactin, and genetically detoxified pertussis toxin (Chiron Biocine). Pertussis was defined as 21 days or more of paroxysmal cough, with infection confirmed by culture or serologic testing.

Results: The efficacy of each vaccine, given in three doses, against pertussis was determined for 14,751 children over an average of 17 months, with cases included in the analysis if cough began 30 days or more after the completion of immunization. For both of the acellular DTP vaccines, the efficacy was 84 percent (95 percent confidence intervals, 76 to 89 percent for Biocine DTP and 76 to 90 percent for SmithKline DTP), whereas the efficacy of the whole-cell DTP vaccine was only 36 percent (95 percent confidence interval, 14 to 52 percent). The antibody responses were greater to the acellular vaccines than to the whole-cell vaccine. Local and systemic adverse events were significantly more frequent after the administration of the whole-cell vaccine. For the acellular vaccines, the frequency of adverse events was similar to that in the control (DT) group.

Conclusions: The two acellular DTP vaccines we studied were safe, immunogenic, and efficacious against pertussis, whereas the efficacy of the whole-cell DTP vaccine was unexpectedly low.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Bacterial / blood
  • Antigens, Bacterial / immunology
  • Antigens, Bacterial / therapeutic use
  • Bordetella pertussis / immunology
  • Diphtheria Toxoid / therapeutic use
  • Diphtheria-Tetanus Vaccine
  • Diphtheria-Tetanus-Pertussis Vaccine / therapeutic use
  • Double-Blind Method
  • Humans
  • Infant
  • Pertussis Toxin
  • Pertussis Vaccine / adverse effects
  • Pertussis Vaccine / immunology
  • Pertussis Vaccine / therapeutic use*
  • Tetanus Toxoid / therapeutic use
  • Treatment Outcome
  • Vaccines, Combined / therapeutic use
  • Vaccines, Inactivated / therapeutic use
  • Virulence Factors, Bordetella / immunology
  • Virulence Factors, Bordetella / therapeutic use
  • Whooping Cough / prevention & control*

Substances

  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Diphtheria Toxoid
  • Diphtheria-Tetanus Vaccine
  • Diphtheria-Tetanus-Pertussis Vaccine
  • Pertussis Vaccine
  • Tetanus Toxoid
  • Vaccines, Combined
  • Vaccines, Inactivated
  • Virulence Factors, Bordetella
  • Pertussis Toxin