A nasal whooping-cough vaccine cleared its first big test in children

Whooping cough is resurgent, and part of the reason is built into the vaccines used against it. The acellular pertussis shots given in most countries protect well against disease but induce weak immunity in the nose and airway, where Bordetella pertussis actually takes hold — so vaccinated people can still carry and transmit it [s1]. A phase 2b trial published in The Lancet Infectious Diseases on October 1 tested a vaccine built to attack that specific gap, in children, with a cautious but positive result [s1].

The idea behind the vaccine

BPZE1 is a live attenuated pertussis vaccine given as nasal drops rather than an injection [s1]. The design goal is mucosal immunity: a secretory IgA (S-IgA) antibody response in the nose that the injected acellular vaccines do not generate [s1]. The hope is that an immune response sited where infection begins could reduce not just illness but carriage and transmission — the part of the problem current boosters leave largely untouched.

The approach already has adult data behind it. An earlier double-blind phase 2b trial in healthy adults aged 18-50 compared BPZE1 with the standard tetanus-diphtheria-acellular pertussis vaccine (Tdap) [s2]. The new trial asked whether the nasal vaccine behaves the same way in acellular-primed children — the group that would matter most for a programme [s1].

The trial

This was a randomised, observer-blinded trial with both placebo and active comparators, run at 16 paediatric research centres — eight in the UK, five in Australia and three in Costa Rica [s1]. Children aged 6 to 17, who had not had a pertussis vaccination or diagnosis in the previous three years, were assigned in equal numbers to one of three groups: nasal BPZE1 with a dummy injection, injected Tdap with nasal placebo, or both the nasal vaccine and Tdap together [s1]. The BPZE1 dose was approximately 10⁹ colony-forming units [s1].

Of 381 children screened between November 11, 2021, and October 24, 2023, 368 were enrolled; 366 were vaccinated — 123 to BPZE1 alone, 121 to BPZE1 plus Tdap, and 122 to Tdap alone — and 354 completed the study [s1]. The mean age was 10.8 years; 196 (54%) were male and 170 (46%) female [s1]. The trial was registered as NCT05116241 and is complete [s3].

What it found

The primary question was whether BPZE1 raised nasal S-IgA against whole-cell B pertussis extract from baseline to day 29, with success defined as the lower limit of the 95% confidence interval for the geometric mean fold rise sitting above 1 in both BPZE1-containing groups [s1]. It did. In the BPZE1-alone group the geometric mean fold rise at day 29 was 3.8 (95% CI 3.1-4.7), and the endpoint was met in both the BPZE1 and BPZE1-plus-Tdap groups [s1].

The second key finding is about interference, and it cuts in the reassuring direction. Giving BPZE1 alongside Tdap did not blunt the Tdap-induced serum IgG response to pertussis antigens, nor the protective responses to diphtheria and tetanus toxoids [s1]. In other words the nasal vaccine can, on this evidence, be added to the existing injected booster without compromising it. BPZE1 was well tolerated across the 7-day reactogenicity window that formed the primary safety outcome [s1].

The caveats, including who paid

Two things keep this result modest. First, the trial measured immune responses, not protection. A rise in nasal S-IgA is a biologically sensible marker for mucosal immunity, but it is not the same as preventing infection, carriage or disease — and the study was neither designed nor sized to show that [s1]. Whether the antibody signal translates into fewer infections, let alone less transmission, is the question the programme still has to answer in far larger efficacy trials.

Second, the trial was funded by ILiAD Biotechnologies, the company developing BPZE1 [s1]. Industry funding of a development-stage trial is standard and does not by itself invalidate a result, but it is exactly the situation in which independent replication and a hard clinical endpoint matter most.

What to watch

Whether efficacy trials powered for infection and transmission follow; whether the mucosal response persists beyond day 29; and whether regulators treat an S-IgA marker as supportive evidence or insist on a disease endpoint before a nasal pertussis vaccine reaches a schedule.

This article describes an early-phase vaccine trial and is informational only. It is not medical advice, and BPZE1 is not an approved vaccine.

Sources

• [s1] Immunogenicity and safety of BPZE1, an intranasal live attenuated pertussis vaccine, evaluated with and without Tdap in healthy children aged 6-17 years: a randomised, phase 2b trial, The Lancet Infectious Diseases, published online 2026-10-01. PMID 42822488. ClinicalTrials.gov NCT05116241. Funded by ILiAD Biotechnologies.
• [s2] Immunogenicity and safety of BPZE1 versus Tdap in healthy adults: a double-blind, phase 2b trial, The Lancet, 2023;401:843-855, published 2023-03-01. PMID 36906345.
• [s3] A Study to Evaluate the Immunogenicity and Safety of BPZE1 in Healthy Children (NCT05116241), ClinicalTrials.gov.