A groundbreaking human challenge trial suggests a novel nasal spray vaccine could revolutionise efforts to curb whooping cough by preventing the bacteria from colonising the nose and throat.

Surge in cases and fatalities

The findings come as England experiences a sharp resurgence in whooping cough, recording the highest number of laboratory-confirmed infections in three decades. According to the UK Health Security Agency’s (UKHSA) Annual Pertussis Report for 2024

• There were 14,879 confirmed cases, the most since enhanced surveillance began in 1994.
• This marked a dramatic rise from 856 cases in 2023.
• The outbreak peaked at 3,034 cases in May before declining to 179 in December.
• Tragically, 11 infants too young to complete their vaccinations died, along with another 11 older individuals, mainly over 60, where pertussis contributed alongside other health issues.

Globally, whooping cough remains highly contagious, causing an estimated 200,000 deaths annually, mostly among unvaccinated children, according to the World Health Organisation.

Limitations of current vaccines

In the UK, routine childhood immunisations include pertussis vaccines at 8, 12, and 16 weeks, plus a preschool booster at three years. However, acellular vaccines

• Lose effectiveness over time
• Fail to provide lifelong immunity
• Do not prevent asymptomatic carriage, which continues to fuel transmission

The COVID-19 pandemic temporarily suppressed cases through social distancing, but numbers rebounded sharply from 2023. Falling maternal vaccination rates, from 64.7% in 2022–2023–58.6% in 2023–2024, further exacerbated the situation.

BPZE1: a potential paradigm shift

BPZE1, developed by ILiAD Biotechnologies, is a live-attenuated strain of Bordetella pertussis administered as a single intranasal spray. Unlike injections, BPZE1 mimics natural infection, training the mucosal immune system in the upper respiratory tract to repel the pathogen at its entry point.

The CHAMPION-1 study, a phase 2b randomised, placebo-controlled trial, tested BPZE1 using a controlled human infection model developed at the University of Southampton within the international PERISCOPE consortium. The trial involved:

• 53 healthy adult volunteers aged 18–50
• Administration of BPZE1 or placebo 2–4 months before deliberate exposure to virulent Bordetella pertussis in a secure quarantine facility
• 16 nights of close monitoring, daily health checks, nasal sampling, and antibiotics to eliminate residual bacteria

Results published in The Lancet Microbe showed BPZE1 was safe, with no serious adverse events, severe nasal symptoms, or systemic reactions. Crucially, vaccinated individuals had significantly reduced bacterial loads in their noses post-challenge, meeting the primary endpoint of protection against colonisation (p=0.033 in sensitivity analysis).

The vaccine also elicited strong immune responses, including nasal secretory IgA antibodies and potent serum bactericidal activity, indicating potential for durable, transmission-blocking protection.

Expert reactions

Professor Robert Read, lead of the study at the NIHR Southampton Biomedical Research Centre, said: “This is the first time a whooping cough vaccine has been shown to prevent the bacteria from colonising the nose and throat in humans. That could represent a big step forward in stopping the spread of the disease.”

Dr Diane Gbesemete, principal investigator at the same centre, added: “Despite high vaccination rates, we’re still seeing outbreaks of whooping cough. This study shows that BPZE1 has the potential to offer better protection and help reduce transmission.”

Public Health Minister Ashley Dalton hailed the trial as: “A major breakthrough in our fight against whooping cough. Unlike the existing vaccine for pregnant women, which protects babies in the womb and prevents nine out of 10 infant deaths, this new nasal spray vaccine works in a completely different way – by stopping the bacteria from living in the nose and throat. That means it could cut transmission and offer longer-lasting protection for everyone, not just newborns. It’s a powerful showcase of the UK’s world-class research sector driving innovation to protect future generations.”

Professor Marian Knight, scientific director for NIHR Infrastructure, emphasised collaboration: “This important research shows how bringing together industry and our world-leading NIHR infrastructure researchers leads to crucial, globally-significant discoveries. This study takes us a step closer to stopping the spread of whooping cough and eventually eradicating it altogether.”

Dr Stephanie Noviello, chief medical officer at ILiAD, said: “These results represent a major milestone in the global public health effort to control whooping cough. For more than a decade, ILiAD has been committed to stopping B. pertussis where it lives – the human upper respiratory tract. We still have a lot of work to do, but this is far and away the best evidence to date that we can fulfil our mission to eradicate all disease due to the bacteria that causes whooping cough. My deep appreciation to everyone who contributed to this study, especially the study participants. Without them, this achievement would not be possible.”

Next steps

ILiAD plans phase 3 trials in 2026 to evaluate BPZE1 in larger populations, potentially paving the way for regulatory approval and broader rollout to adults and children. Preclinical and future clinical studies will also explore its use in pregnancy, although current data for maternal application is not yet available.

Continuing maternal vaccination

The UK’s maternal pertussis vaccination programme, launched in 2012, continues to protect newborns. Administered from 16 weeks of pregnancy, it transfers antibodies to the fetus, achieving 91% effectiveness against infant mortality based on data up to August 2024. Most 2024 infant deaths involved unvaccinated mothers, underscoring the need for vaccine uptake.

Looking ahead

As pertussis cases fell to 335 in early 2025, the BPZE1 trial underscores the urgency of innovation in vaccine-preventable diseases. Experts warn that without tools to interrupt bacterial carriage, cyclical epidemics will continue, particularly threatening vulnerable infants at risk of pneumonia, seizures, and apnoea.

The development highlights the UK’s strength in translational research, combining NIHR-funded infrastructure with industry to tackle resurgent threats like whooping cough.