Groundbreaking vaccination approach could transform respiratory disease prevention

A research team from Trinity College Dublin has unveiled a groundbreaking new approach to vaccination that could redefine how we protect against respiratory infections. In a landmark study published in Nature Microbiology, the team demonstrated that their nasally-delivered, antibiotic-inactivated Bordetella pertussis (AIBP) vaccine not only prevents severe disease but also curbs bacterial transmission - an achievement long sought by vaccine developers worldwide.

The work, led by Professor Kingston Mills and Dr Davoud Jazayeri of Trinity's School of Biochemistry and Immunology, introduces a needle-free mucosal vaccine platform capable of inducing durable local immunity directly at the infection site. This strategy could transform both whooping cough prevention and the broader market for respiratory bacterial vaccines, addressing an urgent global need for next-generation immunisation technologies.

We've applied our understanding of protective immune pathways to engineer a fundamentally different kind of vaccine. 

By stimulating immunity where infections begin, at the respiratory mucosa, we can offer stronger protection and potentially interrupt community transmission."

Professor Kingston Mills, Trinity's School of Biochemistry and Immunology

Current whooping cough vaccines, while life-saving, have key limitations: they protect infants from severe illness but fail to prevent bacterial colonization in the nose and throat, allowing continued spread within communities. Global resurgence of pertussis - despite high vaccination coverage - underscores the commercial and clinical demand for improved vaccines.

The Trinity team's innovation hinges on antibiotic-inactivated Bordetella pertussis delivered intranasally rather than by injection. This delivery route activates a distinct T-cell-driven mucosal immune response that shields both the lungs and upper respiratory tract without triggering unwanted systemic inflammation.

In preclinical studies, AIBP achieved complete protection against infection of the lungs and nasal cavity, which outperforms current acellular pertussis vaccines. These findings suggest AIBP could serve as both a stand-alone next-generation pertussis vaccine and a "plug-and-play" platform adaptable to other pathogens such as Staphylococcus aureus, Streptococcus pneumoniae, Mycoplasma pneumoniae and Mycobacterium tuberculosis.

This research was initially funded through a Research Ireland Frontiers for the Future Award to Prof Mills and is now advancing under the ARC Hub for Therapeutics, a €32 million national translational research initiative administered by Research Ireland and co-funded by the Government of Ireland and the European Union through the ERDF Southern, Eastern & Midland Regional Programme 2021-2027.