A phase 2 randomized controlled dose-ranging trial of recombinant pertussis booster vaccines containing genetically inactivated pertussis toxin in women of childbearing age

Vaccine. 2022 Apr 1;40(15):2352-2361. doi: 10.1016/j.vaccine.2021.10.076. Epub 2021 Nov 14.


Background: A phase 2 randomized-controlled safety and immunogenicity trial evaluating different doses of recombinant acellular pertussis vaccine containing genetically-inactivated pertussis toxin (PTgen) was conducted in women of childbearing age in Thailand to identify formulations to advance to a trial in pregnant women.

Methods: A total of 250 women were randomized 1:1:1:1:1 to receive one dose of one of three investigational vaccines including low-dose recombinant pertussis-only vaccine containing 1 μg PTgen and 1 μg FHA (ap1gen), tetanus, reduced-dose diphtheria (Td) combined to ap1gen (Tdap1gen) or combined to recombinant pertussis containing 2 μg PTgen and 5 μg FHA (Tdap2gen), or one dose of licensed recombinant TdaP vaccine containing 5 μg PTgen and 5 μg FHA (Boostagen®, TdaP5gen) or licensed Tdap vaccine containing 8 μg of chemically inactivated pertussis toxoid (PTchem), 8 μg FHA, and 2.5 μg pertactin (PRN) (BoostrixTM, Tdap8chem). Serum Immunoglobulin G (IgG) antibodies against vaccine antigens were measured before and 28 days after vaccination by ELISA. To advance to a trial in pregnant women, formulations had to induce a PT-IgG seroresponse rate with a 95% confidence interval (95% CI) lower limit of ≥ 50%.

Results: Between 5 and 22 July 2018, a total of 250 women with median age of 31 years were enrolled. Post-vaccination PT-IgG seroresponse rates were 92% (95% CI 81-98) for ap1gen, 88% (95% CI 76-95) for Tdap1gen, 80% (95% CI 66-90) for Tdap2gen, 94% (95% CI 83-99) for TdaP5gen, and 78% (95% CI 64-88) for Tdap8chem. Frequencies of injection site and systemic reactions were comparable between the groups. No serious adverse events were reported during the 28-day post-vaccination period.

Conclusions: All recombinant acellular pertussis vaccines were safe and immunogenic in women of childbearing age, and all met pre-defined immunogenicity criteria to advance to a trial in pregnant women.

Clinical trial registration: Thai Clinical Trial Registry, TCTR20180321004.

Keywords: Genetically-inactivated; Immunogenicity; Low-dose; Non-pregnant; Pertussis; Safety.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Bacterial
  • Diphtheria-Tetanus-Pertussis Vaccine
  • Diphtheria-Tetanus-acellular Pertussis Vaccines*
  • Female
  • Humans
  • Immunization, Secondary
  • Pertussis Toxin / genetics
  • Pregnancy
  • Whooping Cough* / prevention & control


  • Antibodies, Bacterial
  • Diphtheria-Tetanus-Pertussis Vaccine
  • Diphtheria-Tetanus-acellular Pertussis Vaccines
  • Pertussis Toxin

Associated data

  • TCTR/TCTR20180321004