Efficacy, immunogenicity, and safety of the live attenuated nasal pertussis vaccine, BPZE1, in the UK: a randomised, placebo-controlled, phase 2b trial using a controlled human infection model with virulent Bordetella pertussis

Abstract

Background: Pertussis is a severe respiratory disease caused by Bordetella pertussis. Although vaccines prevent disease for a limited duration, they do not prevent infection and transmission. We aimed to assess the safety and efficacy of BPZE1 at preventing or substantially reducing colonisation by virulent B pertussis using a robust controlled human infection model.

Methods: This randomised, placebo-controlled, phase 2b trial was conducted at University Hospital Southampton and University of Oxford in the UK. Eligible participants were healthy adults aged 18-50 years, who complied with the protocol, refrained from smoking and nasal sprays, and were fully vaccinated against SARS-CoV-2. Exclusion criteria were pertussis vaccination or illness (<5 years), baseline anti-pertussis toxin serum IgG (>20 International Units [IU]/mL) or anti-pertactin serum IgG (>30 IU/mL) concentrations, and a positive SARS-CoV-2 test. Participants were randomly assigned (1:1), using permuted blocks with a block size of four, to receive an intranasal dose of 10⁹ colony-forming units (CFU) of BPZE1 or placebo (lyophilised buffer) and were challenged 60-120 days later with 10⁵ CFU virulent B pertussis. Masked staff administered the study vaccine. Nasal mucosal secretion and blood samples were collected. The primary outcome was negative B pertussis cultures of nasal washes at days 9, 11, and 14 after virulent challenge in the modified intention-to-treat (mITT; defined as all participants randomly assigned to treatment who were vaccinated, challenged, and had at least one culture result at day 9, 11, or 14 post-challenge) and per protocol adequate inoculum populations (defined as all participants in the mITT population who received a challenge inoculum equal to or higher than the target (≥0·5 × 10⁵ CFU; sensitivity analysis). This trial is registered with ClinicalTrials.gov, NCT05461131.

Findings: Between June 23, 2022, and Oct 26, 2023, 141 participants were assessed for eligibility, of whom 88 were ineligible and 53 were randomly assigned (26 to the BPZE1 group and 27 to the placebo group). 26 (49%) participants were male and 27 (51%) were female, with a mean age of 30·42 years (SD 8·49). Participants self-identified as White (42 [79%]), Black (six [11%]), or Asian (five [9%]). Five (9%) participants did not receive virulent challenge and two (4%) were lost to follow-up before virulent challenge. 46 (87%) participants received virulent challenge at 60-120 days (24 in the BPZE1 group vs 22 in the placebo group). One in the BPZE1 group withdrew consent and one in the placebo group was not evaluable due to COVID-19. 44 (83%) completed the challenge trial unit stay (23 [88%] vs 21 [78%]). 24 (92%) participants in the BPZE1 group and 21 (78%) in the placebo group were included in the mITT population. In the mITT population, the number of participants with no detectable colonisation on days 9, 11, and 14 post-challenge was higher in the BPZE1 group (14 [58%; 95% CI 39-76] of 24 vs seven [33%; 17-55] of 21 in the placebo group; p=0·091). Four (17%) in the BPZE1 group and five (24%) in the placebo group received a lower challenge dose than the target. In the per protocol adequate inoculum population, 12 (60%; 39-78) of 20 in the BPZE1 group and four (25%; 10-50) of 16 in the placebo group had no detectable colonisation by B pertussis B1917 on days 9, 11, and 14 post-challenge (p=0·033). Most participants reported at least one solicited adverse event during the 7 days after vaccination (22 [85%] of 26 in the BPZE1 group vs 22 [81%] of 27 in the placebo group), which were mostly mild (grade 1) in severity. Unsolicited adverse events were reported in similar frequency in the BPZE1 and placebo groups during the 28 days after vaccination (seven [27%] of 26 vs nine [33%] of 27). No serious adverse events or discontinuations due to adverse events were reported during the trial.

Interpretation: Intranasal BPZE1 vaccination prevented or substantially reduced infection after challenge with virulent B pertussis and is an attractive vaccine candidate. Given the favourable safety profile, large phase 3 trials are warranted to confirm these initial findings.

Funding: ILiAD Biotechnologies.