Otitis media (OM) is a highly prevalent infection of the middle ear and remains the most commonly diagnosed childhood disease among Australian children, with a disproportionate burden of disease and hearing loss observed in Aboriginal and Torres Strait Islander populations. Despite its significant clinical and socioeconomic impact, no licensed vaccine is currently available for OM. Existing pneumococcal conjugate vaccines provide only partial protection, as they do not effectively cover non-vaccine pneumococcal serotypes or other major otopathogens, including non-typeable Haemophilus influenzae and Moraxella catarrhalis. The frequent and often prolonged use of antibiotics for OM management has further contributed to the emergence of antimicrobial resistance, particularly among non-typeable H. influenzae and M. catarrhalis, underscoring an urgent need for alternative preventive strategies. Notably, M. catarrhalis lacks any licensed vaccine antigen, highlighting a critical gap in OM vaccine development.
In this study, we investigated novel, conserved protein antigens from M. catarrhalis that have not been previously explored as vaccine candidates. These antigens were selected based on conservation across strains and predicted immunogenic potential. The target proteins were cloned, heterologously expressed in Escherichia coli, and purified using immobilized metal affinity chromatography to high purity. Purified recombinant proteins were formulated for immunization, and their ability to induce protective immune responses was evaluated in a murine model.
Immunized mice generated robust antigen-specific antibody responses, as demonstrated by whole-cell ELISA against both homologous and heterologous M. catarrhalis strains. IgG isotyping revealed a predominantly Th1-biased immune response, accompanied by a moderate Th2 component, suggesting the induction of balanced and functionally relevant immunity. Importantly, sera from immunized mice exhibited strong bactericidal activity against multiple M. catarrhalis strains in serum bactericidal assays, indicating the functional capacity of the elicited antibodies to mediate bacterial killing. Specificity of the immune response induced was further evaluated by Westen blot which showed that murine antisera was capable of detecting the target proteins in a wide panel of clinical isolates of M. catarrhalis.
Collectively, these findings demonstrate that novel conserved protein antigens from M. catarrhalis can induce broad and functional immune responses, supporting their potential as promising components of a protein-based vaccine strategy for the prevention of otitis media.