Multi-Antigen Protein Vaccine Confers Protection in a Murine Model Against Intranasal Haemophilus influenzae Challenge.

Background: Non-typeable Haemophilus influenzae (NTHi) is a major cause of acute respiratory tract infections and chronic airway disease, despite its clinical importance, no licensed vaccine is available, largely due to the extensive genetic and antigenic diversity among circulating isolates. We previously identified conserved outer membrane proteins capable of inducing systemic protection against NTHi. Methods: In this study, we evaluated whether a multi-antigen protein vaccine composed of conserved NTHi antigens (P5 and P26) could protect against pulmonary infection. Transgenic mice expressing human transferrin and factor H were immunized via the intraperitoneal or intranasal route and challenged intranasally with a clinical NTHi isolate. Bacterial clearance, antigen-specific mucosal and systemic antibody responses, and recruitment of innate immune cells to the airways were assessed. Results: Both immunization routes significantly reduced bacterial loads compared with controls. Vaccination induced robust mucosal and systemic IgG and IgA responses and enhanced early recruitment of macrophages, monocytes, dendritic cells, and neutrophils to the airways. Intranasal immunization elicited strong mucosal antibody responses and was associated with improved local bacterial clearance. Conclusions: These findings demonstrate that multi-antigen vaccines targeting conserved NTHi proteins can elicit effective mucosal and systemic immunity and represent promising candidates for the prevention against NTHi respiratory infections.