Nasal Delivery of Haemophilus haemolyticus Is Safe, Reduces Influenza Severity, and Prevents Development of Otitis Media in Mice

Naomi Scott; Kelly M Martinovich; Caitlyn M Granland; Elke J Seppanen; M Christian Tjiam; Camilla de Gier; Edison Foo; Kirsty R Short; Keng Yih Chew; Alma Fulurija; Deborah H Strickland; Peter C Richmond; Lea-Ann S Kirkham

doi:10.1093/infdis/jiae069

Nasal Delivery of Haemophilus haemolyticus Is Safe, Reduces Influenza Severity, and Prevents Development of Otitis Media in Mice

J Infect Dis. 2024 Mar 12:jiae069. doi: 10.1093/infdis/jiae069. Online ahead of print.

Authors

Naomi Scott¹, Kelly M Martinovich^{1

2}, Caitlyn M Granland¹, Elke J Seppanen¹, M Christian Tjiam^{1

2}, Camilla de Gier¹, Edison Foo¹, Kirsty R Short^{3

4}, Keng Yih Chew³, Alma Fulurija^{1

2}, Deborah H Strickland^{1

2}, Peter C Richmond^{1

5}, Lea-Ann S Kirkham^{1

2}

Affiliations

¹ Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Western Australia.
² Centre for Child Health Research, University of Western Australia, Perth.
³ School of Chemistry and Molecular Biosciences, Faculty of Science, University of Queensland, Brisbane.
⁴ Australian Infectious Diseases Research Centre, Global Virus Network Centre of Excellence, Brisbane, Queensland.
⁵ Department of Paediatrics, School of Medicine, University of Western Australia, Perth, Australia.

PMID: 38470272
DOI: 10.1093/infdis/jiae069

Abstract

Background: Despite vaccination, influenza and otitis media (OM) remain leading causes of illness. We previously found that the human respiratory commensal Haemophilus haemolyticus prevents bacterial infection in vitro and that the related murine commensal Muribacter muris delays OM development in mice. The observation that M muris pretreatment reduced lung influenza titer and inflammation suggests that these bacteria could be exploited for protection against influenza/OM.

Methods: Safety and efficacy of intranasal H haemolyticus at 5 × 107 colony-forming units (CFU) was tested in female BALB/cARC mice using an influenza model and influenza-driven nontypeable Haemophilus influenzae (NTHi) OM model. Weight, symptoms, viral/bacterial levels, and immune responses were measured.

Results: Intranasal delivery of H haemolyticus was safe and reduced severity of influenza, with quicker recovery, reduced inflammation, and lower lung influenza virus titers (up to 8-fold decrease vs placebo; P ≤ .01). Haemophilus haemolyticus reduced NTHi colonization density (day 5 median NTHi CFU/mL = 1.79 × 103 in treatment group vs 4.04 × 104 in placebo, P = .041; day 7 median NTHi CFU/mL = 28.18 vs 1.03 × 104; P = .028) and prevented OM (17% OM in treatment group, 83% in placebo group; P = .015).

Conclusions: Haemophilus haemolyticus has potential as a live biotherapeutic for prevention or early treatment of influenza and influenza-driven NTHi OM. Additional studies will deem whether these findings translate to humans and other respiratory infections.

Keywords: Haemophilus haemolyticus; NTHi; influenza; intranasal therapy; otitis media.

Abstract

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