Nasal Vaccine Could Curb Whooping Cough Transmission and Boost Local Immunity

A research team at Trinity College Dublin has developed an innovative nasal vaccine against Bordetella pertussis (whooping cough) that not only protects against disease but also blocks infection of the upper respiratory tract. The preclinical trial data were published in Nature Microbiology and support continued research of alternative respiratory immunization methods.¹

“We’ve applied our understanding of protective immune pathways to engineer a fundamentally different kind of vaccine,” said Kingston Mills, PhD, professor at Trinity’s School of Biochemistry and Immunology. “By stimulating immunity where infections begin, at the respiratory mucosa, we can offer stronger protection and potentially interrupt community transmission.”²

Whooping cough is a highly contagious respiratory infection that poses the greatest danger to infants, particularly those under 6 months of age. In this group, the illness can lead to severe complications, long-term health effects, and even death. Characterized by its signature “100-day cough,” pertussis can affect people of all ages, but its impact is especially severe in young children whose smaller lungs and airways make it harder to breathe during prolonged coughing fits.³

Although acellular pertussis (aP) vaccines effectively reduce severe illness, they fall short in preventing nasal colonization and onward transmission. The intranasal vaccine uses antibiotic-inactivated bacteria (AIBP), delivered via aerosol or intranasal routes, to stimulate tissue-resident memory T cells and mucosal IgA responses in the respiratory tract.¹

In preclinical studies in mice, the AIBP vaccine, derived from ciprofloxacin-treated B. pertussis, showed strong activation of antigen-presenting cells and induced robust CD4 T cell responses of the TH1 and TH17 varieties. Immunized animals cleared bacteria from both lungs and nasal tissue. Following 2 immunizations, the nasal infection was completely cleared by day 14—an outcome not achieved with current intramuscular whole-cell pertussis (wP) or aP vaccines.¹

“Our approach of using ciprofloxacin-treated B. pertussis has significant advantages over current aP vaccines and combines the benefits of live attenuated pertussis vaccines and wP vaccines,” the researchers wrote, “but with low risks and high immunogenicity when delivered to the respiratory tract.”¹

Mechanistic experiments confirmed that when either CD4 T cells or IL-17 were blocked, the vaccine’s effect was lost. Aerosol delivery of the AIBP vaccine did not trigger the systemic inflammatory responses observed with wP vaccination—suggesting a favorable safety profile. The researchers note that prior immunization with aP vaccines did not impede the effectiveness of the AIBP platform, suggesting potential as a booster in already-vaccinated individuals.¹

A nasal immunization strategy presents several advantages. It targets the primary site of infection and transmission (the nasal passages) and raises local immune defenses (IgA, tissue-resident T cells). Beyond that, it is needle-free—an attractive characteristic for patients who may struggle with injections.¹

Given the resurgence of pertussis in many regions despite high vaccine coverage, the ability to block colonization and transmission is a major step forward. This research offers preclinical proof-of-concept that a needle-free, respiratory-delivered vaccine can prevent infection, not just disease, by mobilizing mucosal T-cell/IgA immunity at the source.

REFERENCES

1. Jazayeri SD, Borkner L, Sutton CE, et al. Respiratory immunization using antibiotic-inactivated Bordetella pertussis confers T cell-mediated protection against nasal infection in mice. Nat Microbiol. November 10, 2025. Doi: 10.1038/s41564-025-02166-6

2. New nasal vaccine has potential to transform respiratory disease prevention. News Release. November 10, 2025. Accessed November 12, 2025. https://www.eurekalert.org/news-releases/1105131

3. Halpern L. What to Know about the latest pediatric respiratory infections. Pharmacy Times. October 22, 2025. Accessed November 12, 2025. https://www.pharmacytimes.com/view/what-to-know-about-the-latest-pediatric-respiratory-infections