A novel TamA + LtgC bivalent vaccine induces potent immunogenic and bactericidal antibodies against Neisseria gonorrhoeae.

Development of an effective vaccine against Neisseria gonorrhoeae comes with unique challenges. After five decades of research, the lack of an FDA-approved vaccine underscores the need for novel immunization strategies. Therefore, in this study, we evaluated a bivalent vaccine compared to two single-antigen formulations containing LtgC or TamA. The tamA and ltgC genes were cloned, expressed and purified. Serum IgG levels against recombinant proteins in gonorrhea patients were assessed by the enzyme-linked immunosorbent assay (ELISA). Mice were immunized with TamA and/or LtgC formulations alongside Monophosphoryl-lipid A (MPLA) adjuvant. Serum and vaginal IgG and IgA levels were measured. Then, the serum bactericidal assay (SBA), and opsonophagocytic activity (OPA) assays were performed. The presence of antigen-specific antibodies in patients’ sera indicates that the recombinant proteins elicit immune responses in natural infection. All formulations elicited robust long-lasting systemic IgG responses, with TamA + MPLA inducing the highest IgG titers. The bivalent formulation showed superior IgA responses in serum, while in vaginal wash, its superiority was not evident. TamA + MPLA and the bivalent formulation showed comparable higher SBA and OPA titers compared to the LtgC + MPLA. TamA and LtgC monovalent formulations induced long-lasting antibodies, with desirable bactericidal effects. TamA + MPLA and the combination group exhibited similar SBA and OPA titers. Despite the half-dose of TamA in the combination, inclusion of LtgC appears to enhance serum bactericidal activity. Thus, future investigations should focus on dose optimization to maximize synergistic effects of the bivalent formulation.