Preclinical Evaluation of a Microneedle-Delivered Adjuvanted Microparticulate Gonorrhea Vaccine in Non-Human Primates.

Background/Objectives: Gonorrhea remains one of the most prevalent sexually transmitted infections globally, with an estimated 82-87 million new infections annually and no licensed vaccine available. Antigenic variability and the lack of durable protective immunity following natural infection have been major obstacles to vaccine development. We previously developed an adjuvanted, formalin-inactivated whole-cell gonococcal microparticle (GC-MP) vaccine delivered by dissolving microneedles and demonstrated that it induced functional antibodies and enhanced bacterial clearance in murine models. Here, we evaluated this GC-MP microneedle platform in Rhesus macaques to provide proof-of-concept data in a relevant large-animal model and to compare different adjuvants. Methods:Rhesus macaques were allocated into five groups and vaccinated, and serum antigen-specific IgG and IgA responses were quantified by ELISA, with functional activity assessed by serum bactericidal assay. In parallel, the potency of delta-inulin-, aluminum-phosphate-, or aluminum-hydroxide-adjuvanted N. gonorrhoeae-loaded microparticles to activate dendritic cells was assessed in vitro via changes in surface expression of MHC I, MHC II, CD40, and CD80. Results: The serum from vaccinated primates demonstrated elevated gonococcal-specific IgG and IgA responses compared with naïve controls and measurable bactericidal activity against live, homologous N. gonorrhoeae strains. All adjuvanted formulations increased dendritic cell expression of MHC I, MHC II, CD40, and CD80. Conclusions: These findings indicate that an adjuvanted whole-cell inactivated gonorrhea vaccine delivered transdermally via microneedles elicits clearly elevated, relative to controls, functional antibody responses, supporting its advancement toward clinical evaluation.