Nontypeable Haemophilus influenzae (NTHi) is a major otitis media (OM) pathogen and there are no vaccines available. We have identified that intranasal delivery of the human upper respiratory tract commensal Haemophilus haemolyticus can protect mice against NTHi colonisation and subsequent development of OM.
BALB/c mice were intranasally administered 5×107 CFU H. haemolyticus (Day -1) then subjected to the NTHi OM model that uses co-infection with 1×104.5 PFU influenza A virus on Day 0 followed by intranasal challenge with 5×107 CFU of NTHi on Day 3. NTHi viable counts and H. haemolyticus qPCR, inflammatory mediators (interleukin-1β [IL-1β], IL-6 IFN-γ and keratinocyte chemoattractant [KC]) were measured in nasal washes and middle ear tissue collected on Day 5 and Day 7. Clinical scores and weight were monitored throughout.
NTHi colonisation titres were reduced in mice that received a single intranasal dose of H. haemolyticus, with only one of the treated mice developing low density NTHi OM. Colonisation of mice with H. haemolyticus was not detected by qPCR on Day 5 or Day 7. We have identified a human commensal that can prevent the development of NTHi OM in a preclinical animal model. Given the burden of NTHi OM and unmet need for effective prevention strategies, human studies are warranted.