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

Introduction: Despite a decrease in infections caused by Bordetella pertussis due to COVID-19 pandemic, booster vaccination of pregnant women is still recommended to protect newborns. Highly immunogenic vaccines containing genetically inactivated pertussis toxin (PT _gen ) and filamentous hemagglutinin (FHA) may generate comparable anti-PT antibody concentrations, even at lower doses, to chemically inactivated acellular pertussis vaccines (Tdap _chem ) shown effective for maternal immunization.
Methods: This phase 2 randomized, observer-blind, active-controlled non-inferiority trial was conducted in healthy Thai pregnant women randomly assigned to receive one dose of low-dose recombinant pertussis-only vaccine containing 1 µg PT _gen and 1 µg FHA (ap1 _gen ), or tetanus, reduced-dose diphtheria combined with ap1 _gen (Tdap1 _gen ), or combined with 2 µg PT _gen and 5 µg FHA (Tdap2 _gen ), or with 5 µg PT _gen and 5 µg FHA (TdaP5 _gen , Boostagen®) or comparator containing 8 µg of chemically inactivated pertussis toxoid, 8 µg FHA, and 2.5 µg pertactin (Boostrix™, Tdap8 _chem ). Blood was collected at Day 0 and Day 28 post-vaccination. The non-inferiority of the study vaccines was assessed based on anti-PT IgG antibody levels on Day 28 pooled with results from a similarly structured previous trial in non-pregnant women.
Results: 400 healthy pregnant women received one dose of vaccine. Combined with data from 250 non-pregnant women, all study vaccines containing PT _gen were non-inferior to comparator vaccine (Tdap8 _chem ). Both ap1 _gen and TdaP5 _gen vaccines could be considered to have superior immunogenicity to Tdap8 _chem . Local and systemic solicited reactions were similar among all vaccine groups.
Conclusions: Vaccine formulations containing PT _gen were safe and immunogenic in pregnant women. The ap1 _gen vaccine, with the lowest cost and reactogenicity, may be suitable for use in pregnant women when diphtheria and tetanus toxoids are not needed. This study is registered in the Thai Clinical Trial Registry (www.
Clinicaltrials: in.th), number TCTR20180725004.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Librada Fortuna, Chawanee Kerdsomboon, Vilasinee Yuwaree, Souad Mansouri and Pham Hong Thai are employed by BioNet. All other authors declare no competing interests.
(Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)