Even a single dose of AIBP demonstrates substantial protection and outperforms current acellular vaccines in preventing nasal infection.

The AIBP platform inactivates B. pertussis with ciprofloxacin to preserve cellular structures and epitopes, enabling robust mucosal T cell–driven protection against respiratory infection.

Post-immunization, there is an rise in Th17 and Th1 CD4+ T cells, enhancing mucosal barrier function and microbial clearance, with tissue-retaining T cells supporting long-term immunity.

Protection is primarily mediated by T cells rather than antibodies, with tissue-resident memory T cells in the nasal mucosa driving rapid, localized responses upon exposure.

Delivery is needle-free and mucosal, designed to elicit durable local immunity at the infection site and foster a T-cell–driven response with limited systemic inflammation.

The nasal, aerosol-like administration not only strengthens protection against nasal infection but also has potential to interrupt community spread of pertussis and other respiratory pathogens.

The vaccine works by delivering mucosal immunity via the nasal route, aiming to generate strong local T cell responses and IgA production with minimal systemic inflammation.

Future work will assess how durable mucosal T cell memory is, booster needs, and where exactly in the respiratory tract the vaccine should be delivered to maximize protection.

In preclinical models, intranasal AIBP provides superior protection against nasal infection compared to current vaccines, with efficacy linked to local IL-17 and IFN-γ–producing TRM cells and nasal IgA.

Compared with whole-cell vaccines, AIBP yields stronger mucosal IgA and TRM responses in the respiratory tract, while whole-cell vaccines induce stronger systemic IgG but less mucosal protection.

A Trinity College Dublin team has developed a novel intranasal vaccine for pertussis, using antibiotic-inactivated Bordetella pertussis (AIBP) to prevent severe disease and, importantly, reduce nasal carriage and transmission.

The AIBP platform is a programmable, plug-and-play system potentially adaptable to other pathogens, offering broader applications beyond pertussis.

Lead researchers describe the approach as targeting the respiratory mucosa to achieve stronger protection without systemic inflammation, presenting a fundamentally different vaccine paradigm.

Safety profile appears favorable with limited systemic inflammation and no respiratory tract colonization observed in mice after aerosol or intranasal delivery.

This mucosal strategy focuses on blocking nasal colonization and transmission rather than just preventing disease, signaling a shift from traditional acellular vaccines.

If effective in humans, the nasal AIBP vaccine could reduce transmission and broaden protection, addressing urgent global demand for next-generation respiratory vaccines.

Preclinical studies show AIBP provides complete protection in both lungs and nasal passages, with two-dose regimens via aerosol achieving sterilizing immunity.

AIBP robustly generates B. pertussis–specific CD4+ tissue-resident memory cells in lungs and nasal tissues, producing IFN-γ and IL-17, along with antigen-specific nasal IgA, correlates of protection against colonization.

Funding and support include a Research Ireland Frontiers for the Future Award and ongoing development under a €32 million ARC Hub for Therapeutics, spanning 2021–2027.

If translated to humans, mucosal, T cell–driven immunity could block transmission and help achieve herd immunity, reshaping next-generation vaccines for pertussis and other mucosal pathogens.

AIBP maintains efficacy in mice primed with conventional aP vaccines, showing compatibility and additive benefits with existing immunization strategies.

Context: Current pertussis vaccines mainly prevent severe disease but do not prevent nasal colonization or transmission, underscoring the need for vaccines that block infection at the entry point.

Translational steps include validating in human trials, optimizing inactivation to preserve T cell epitopes, refining mucosal delivery formulations, and exploring combinations with existing vaccines.

Durable mucosal immunity is indicated, with AIBP-induced protection and TRM responses remaining elevated for months after immunization and challenge.

In vivo data show significantly lower bacterial loads in nasal tissues of immunized mice after live B. pertussis challenge, indicating effective prevention of colonization.

The vaccine uses antibiotic inactivation to stop replication while preserving antigenic structures and is delivered to engage the mucosal immune system.

AIBP activates local antigen-presenting cells and drives Th1/Th17 responses in the respiratory tract, including IL-1β, IL-12p70, and IL-23, with minimal systemic inflammation.

Key researchers include Kingston Mills and Davoud Jazayeri, and the findings were published in Nature Microbiology in 2025, with the DOI 10.1038/s41564-025-02166-6.