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.