Mucosal immune cell priming by intranasally delivered Haemophilus haemolyticus is associated with heterologous protection against influenza and nontypeable Haemophilus influenzae.

Authors

Jack S Pepper, Caitlyn M Granland, Sharon L Clark, Ruth B Thornton, Josephine Bayliss, M Z Edison Foo, Wesley Billingham, Naomi Scott, Alma Fulurija, Deborah H Strickland, Selma P Wiertsema, Peter C Richmond, Elke J Seppanen, Lea-Ann S Kirkham, M Christian Tjiam

Published in

Frontiers in immunology. Volume 17. Pages 1855464. Epub Jul 20, 2026.

Abstract

Intranasal vaccines offer a needle-free strategy to enhance immunity to respiratory infections. We investigated the mechanism of action of a novel intranasal vaccine using the human respiratory commensal Haemophilus haemolyticus (Hh), previously shown to protect against nontypeable Haemophilus influenzae (NTHi) otitis media and accelerate clearance of influenza A virus (IAV).
Mucosal and systemic cellular immune responses were assessed 2-144 hours after intranasal Hh treatment in mice, compared with placebo or the Toll-Like Receptor (TLR)2-6 agonist Pam2CSK4 using spectral flow cytometry. The impact of treatment on subsequent IAV and NTHi challenge was also evaluated.
Hh induced a distinct, tissue-specific immune signature with rapid recruitment of neutrophils and inflammatory monocytes to the lungs, peaking at 6 hours, earlier than Pam2CSK4. Hh also generated higher proportions of nasal CD103⁺CD4⁺ T cells within 48 hours, which further expanded following sequential IAV and NTHi infection.
These findings demonstrate that Hh primes mucosal immune responses to promote heterologous protection.

PMID:
42548815
Bibliographic data and abstract were imported from PubMed on 04 Aug 2026.

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