MlaA, a conserved outer membrane protein of Neisseria gonorrhoeae, elicits potent functional immunity and protects against vaginal infection as a mucosal vaccine candidate.

The global spread of multidrug-resistant Neisseria gonorrhoeae strains presents a major challenge in the treatment of gonorrhoea. Vaccination represents a promising long-term strategy for disease control. However, no licensed vaccine is currently available. In this study, we investigated MlaA as a potential vaccine candidate antigen by assessing its endogenous expression, immunogenicity, and the functional activity of induced antibodies. Our findings show that the gene encoding MlaA is highly conserved, and expressed across all tested strains of N. gonorrhoeae. Intranasal immunization of mice with recombinant MlaA-TF and CTB adjuvant elicited robust Th1, Th2, and Th17 immune responses, characterized by a predominance of IgG1 antibodies. The induced anti-MlaA-TF antibodies were functionally active, mediating bacterial killing through high-titer serum bactericidal activity (1:1600, P ≤ 0.0001) and opsonophagocytic activity (1:3200, P ≤ 0.0001). Furthermore, these antibodies significantly inhibited the association of N. gonorrhoeae with ME-180 epithelial cells. In a mouse vaginal infection model, the clearance efficacy of the MlaA-TF vaccine was significantly superior to that of the control (PBS, pCold TF). Our findings demonstrate that MlaA is a highly conserved and immunogenic antigen capable of inducing functional, protective immunity, supporting its further development as a component of a gonococcal vaccine.