Immunogenicity and safety of BPZE1, an intranasal live attenuated pertussis vaccine, evaluated with and without tetanus-reduced diphtheria-acellular pertussis vaccine in healthy children aged 6-17 years: a randomised, active-controlled and placebo-controlled, phase 2b trial

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• Picked for Pediatrics and Child Health (top studies of the week, 4 October 2026): Immunogenicity and safety of BPZE1, an intranasal live attenuated pertussis

Abstract

BACKGROUND: Pertussis remains an important public health issue, in part because current vaccines fail to induce potent mucosal immunity against the causative agent, Bordetella pertussis. In contrast, the live attenuated vaccine BPZE1 induces robust nasal secretory IgA (S-IgA) and protects against B pertussis infection in adults primed with whole-cell vaccines. We evaluated safety and immunogenicity of BPZE1 administered either alone or with tetanus-reduced diphtheria-acellular pertussis vaccine (Tdap) in children primed with acellular pertussis vaccines. METHODS: In this randomised, observer-blinded, placebo-comparator and active-comparator-controlled, phase 2b trial, conducted at 16 paediatric hospital-based research centres and academic clinical sites (eight in the UK, five in Australia, and three in Costa Rica), children aged 6-17 years were randomly assigned by an interactive response technology system using permuted blocks of three (1:1:1 ratio) to receive approximately 109 colony-forming units of BPZE1 intranasally with intramuscular placebo, intramuscular Tdap with intranasal placebo, or BPZE1 plus Tdap. Eligible participants had not received pertussis vaccination or been diagnosed with pertussis in the past three years. The primary immunogenicity outcome was geometric mean fold rises (GMFRs) in nasal S-IgA to whole-cell extract from baseline to day 29 in the per-protocol immunogenicity analysis set, with the outcome met if the lower limit of the 95% CI for the GMFR was greater than 1 for both BPZE1 and BPZE1 plus Tdap groups. The key secondary immunogenicity outcome was baseline-adjusted day 29 geometric mean ratios (GMRs) of anti-acellular pertussis vaccine antigen serum IgG levels between the BPZE1 plus Tdap and Tdap groups, and differences between these groups in percentages of participants with seroprotective antibody concentrations (≥0·1 IU/mL) against diphtheria and tetanus toxoids. Reactogenicity was evaluated through the 7 days after vaccination (primary safety outcome), unsolicited adverse events for 28 days post-vaccination, and serious adverse events throughout the study. The trial was registered at ClinicalTrials.gov (NCT05116241) and is complete. FINDINGS: Between Nov 11, 2021, and Oct 24, 2023, 381 children aged 6-17 years were screened, of whom 368 were enrolled in the study and randomly assigned to receive study vaccine. Two participants were not vaccinated, and 366 received either intranasal BPZE1 and intramuscular placebo (n=123), intranasal BPZE1 and intramuscular Tdap (n=121), or intranasal placebo and intramuscular Tdap (n=122). 354 participants completed the study. Overall, the mean age was 10·8 years (SD 2·79), 196 (54%) were male and 170 (46%) were female, and most participants were categorised as other race (176 [48%]) or White (161 [44%]). The primary endpoint of S-IgA induction was met for B pertussis whole-cell extracts (WCE) in the BPZE1 (n=111) and BPZE1 plus Tdap (n=113) groups, with GMFRs at day 29 post-vaccination of 3·8 (95% CI 3·1-4·7; p<0·0001) and 3·5 (2·9-4·3; p<0·0001), respectively. BPZE1 plus Tdap induction of serum IgG against all acellular pertussis antigens was comparable with those induced by Tdap at day 29, with GMRs of 1·5 (95% CI 1·1-2·1), 1·1 ( 0·9-1·4), and 1·1 ( 0·9-1·4), for anti-pertactin, anti-filamentous haemagglutinin, and anti-pertussis toxin, respectively. All participants (100%) in both Tdap groups had protective anti-diphtheria and anti-tetanus toxoid antibody levels of 0·1 IU/mL or greater at day 29. Solicited adverse events occurred in 59 (48%) of 123, 81 (67%) of 121, and 88 (72%) of 122 participants in the BPZE1, BPZE1 plus Tdap, and Tdap groups, respectively, and events were predominantly mild to moderate. Frequencies of unsolicited adverse events were similar across groups. No vaccine-related serious adverse events, deaths, or adverse events leading to study discontinuation were reported. INTERPRETATION: BPZE1 was well tolerated in children aged 6-17 years, and induced robust nasal S-IgA responses to B pertussis WCE without interference from simultaneously administered Tdap. BPZE1 vaccination did not interfere with Tdap-induced serum IgG to B pertussis antigens and tetanus and diphtheria toxoids. These findings support further development of BPZE1 as a vaccine candidate against pertussis in acellular pertussis vaccine-primed children 6 years and older. FUNDING: ILiAD Biotechnologies, Weston, FL, USA. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Abstract as published, via PubMed.