Project 3 -Translational development of a microneedle patch gonorrhea vaccine (CIIG)

Henry M. Jackson Fdn For The Adv Mil/Med, Rockville MD

Investigators

Abstract

Project 3 – Translational Development of a Microneedle Patch Gonorrhea Vaccine Driven by the major public health threat posed by the emergence of untreatable gonorrhea due to emerging gonococcal antimicrobial resistance, the Centers for Disease and Control Prevention (CDC) have prioritized the need for effective, broadly accessible gonorrhea vaccines. The goal of this translational project is to develop an efficacious, safe, and widely deployable skin immunization platform that induces broadly protective and durable immune responses against Neisseria gonorrhoeae (Ng) infection. Our rapidly translatable cutaneous vaccination strategy exploits novel bacterial outer membrane vesicle (OMV)-based antigen (Ag) constructs, recombinant Ng antigens, and emerging potent and safe adjuvants, as well as needle-free, thermostable, and self-administered microneedle patches (MNPs) for spatially and temporally controlled harnessing of highly immunoresponsive skin microenvironments. We will work seamlessly with the Cores and other Research Projects of the CIIG to bring together transformative project components: 1) skin immunization, 2) emerging skin adjuvants, and 3) dissolving MNPs, with rationally designed and engineered Ng antigen constructs to enable the achievement of the overall goals of the Project 3 and the CIIG. Our preliminary and published data support the innovative features of MNP-directed skin vaccination and demonstrate the key efficacy, safety, immunogenicity, and stability advantages of MNP vaccines over traditional needle and syringe (N&S) vaccines. We will leverage our expertise in MNPs, skin immunobiology, vaccinology, and ex vivo human skin vaccination models, and complement this with the strengths of the Cores and other Research Projects of the CIIG for the development of effective and durable MNP-based Ng vaccines. MNP-directed skin vaccination will significantly improve the magnitude, breadth, and longevity of gonorrhea vaccine-specific protective humoral and cellular responses over traditional N&S vaccines. Compared to N&S vaccines, stable and self-applied MNP-based gonorrhea vaccines will enable more effective, equitable, and sustainable vaccination campaigns against Ng infections. A globally accessible, effective gonorrhea vaccine would have major benefits, such as 1) reduction of number of gonorrhea cases; 2) reduction of detrimental impacts of Ng infections; 3) improvement in SRH and reduction of the spread of HIV infections; and 4) decrease of antimicrobial usage and associated unintended consequences. The new knowledge and vaccination methods generated in this project will be broadly useful for globally effective immunization against a wide range of sexually transmitted infections. Ultimately, this project will result in a globally accessible, clinical trial-ready MNP-based Ng vaccine capable of generating robust systemic and mucosal immune responses that confer durable protection against Ng infection.