Evaluating the Hia adhesin as a potential vaccine antigen against Nontypable Haemophilus influenzae 2309156

Abstract

Abstract Introduction Nontypable Haemophilus influenzae (NTHi) is a major cause of respiratory tract disease, prompting ongoing vaccine development efforts. Nasopharyngeal colonization is the initial step in NTHi pathogenesis, making bacterial adhesins attractive vaccine targets. Hia (Haemophilus influenzae adhesin) is a conserved, surface-exposed protein present in a substantial percentage of NTHi clinical isolates and promotes adherence to respiratory epithelial cells. While the Hia passenger domain (HiaPD) exhibits sequence variability, the Hia binding domain (HiaBD1) is highly conserved across diverse strains. The capacity of HiaPD and HiaBD1 to elicit protective immune responses has not been determined. Methods BALB/c mice were immunized intranasally with purified recombinant HiaPD or HiaBD1 formulated with the adjuvant dmLT and challenged with homologous or heterologous NTHi strains. Bacterial burdens were quantified in nasal tissue. Antigen-specific antibody responses were measured in serum and mucosal samples. Cellular immune responses were evaluated in nasal and lung tissues using flow cytometry to characterize CD4+ T cells activation and cytokine production. Results Intranasal immunization with HiaPD or HiaBD1 significantly reduced nasal bacterial burdens compared to adjuvant controls. Immunized mice developed robust Hia-specific systemic and mucosal antibody responses. Agglutination assays and whole-bacteria ELISA revealed largely strain-specific antibody responses. Passive antibody transfer using sera from HiaPD-immunize mice showed a significant but partial reduction in bacterial burden following homologous challenge. Conclusion These findings demonstrate that the Hia adhesin elicits protective immune responses against NTHi following mucosal immunization. Hia-specific antibodies contribute to protection against homologous challenge , while CD4+ T cell responses likely support protection across diverse strains. Funding Source n/a Topic Categories Vaccines and Immunotherapy (VAC)