EXPLORING PAIN FREE VACCINATION ALTERNATIVES FOR A WHOLE CELL INACTIVATED MICROPARTICULATE GONORRHEA VACCINE

Abstract

There is a global rise in the number of cases of gonorrhea infection each year. Gonorrhea is caused by the bacteria Neisseria gonorrhoeae and is currently being treated using antibiotics. However, this bacterium has gradually developed antimicrobial resistance. Currently, there is no vaccine for gonorrhea. The long-term goal of this project is to formulate and evaluate a microparticulate vaccine against Neisseria gonorrhoeae. The approach taken utilizes the whole cell (formalin-inactivated) as an antigen encapsulated in a microparticulate vehicle and administered painlessly- transdermally via a dissolving microneedle patch, buccally via an oral dissolving film and intranasally via microparticles. The central hypothesis is that by keeping the bacteria whole and intact, with all the antigenic epitopes in their native form, could trigger an immune response and generate specific protective antibodies. To improve uptake of the antigen by immune cells, the whole cell was entrapped in a biodegradable particulate matrix, which are better engulfed by antigen-presenting cells (APCs). Additionally, the use of a sustained release polymer protects the antigen until it is processed by APCs and exposes the antigen to the immune system for an extended period. Transdermal delivery of the vaccine was assessed through dissolving microneedles. Dissolving microneedles were formulated through extensive screening of polymers and sugars to produce fast-dissolving microneedles to effectively deliver the vaccine through the skin. The vaccine was assessed in vivo in a preclinical murine model. This study explored the different doses, cross-protectivity, and memory response for our gonorrhea vaccine candidate when administered as transdermal microneedles. We compared the dose-response strategy, in vivo immunogenicity, correlates of protection, resistance to infection, reinfection, and memory response of our novel gonorrhea vaccine. There was cross-protection against a heterologous strain. Additionally, the vaccine generated humoral, cellular and memory response. Our findings indicate longevity and cross-protection upon vaccination with our transdermal gonorrhea vaccine candidate. This study also explored different pain-free routes for delivering our gonorrhea vaccine candidate. We compared the in vivo immunogenicity, correlates of protection, and resistance to infection of our novel gonorrhea vaccine. All the routes generated strong immunity. Moreover, the transdermal route generated a significantly more robust systemic immune response when compared to all other vaccine routes—the intranasal and buccal mucosal routes generated significantly higher mucosal immunity. The immune responses induced by the pain-free strategies were comparable to the conventional intramuscular route. Our findings indicate the route of administration of the vaccine affects the type of immune responses generated. The overarching goal of this proposal is to address the urgent need of an effective vaccination strategy against gonorrhea, harnessing work from previously funded research by NIH.