Gonococcal vaccine initiative (360G-Wellcome-214374_Z_18_Z)

Neisseria gonorrhoeae (Ng), a leading cause of STI and co-factor for HIV transmission, has developed extensive antimicrobial resistance. Therefore innovative measures to combat Ng are urgently required. While vaccines have been remarkably effective for preventing bacterial infection, there has been scant progress towards Ng vaccines. However, recent advances provide the first prospects for success in decades. We will exploit these advances and our expertise to validate effective antigens for inclusion in a gonococcal vaccine through five related aims. We will :- 1) identify Ng antigens through a clinical trial of an outer membrane vesicle (OMV)-containing vaccine from Neisseria meningitidis as an immunological probe in an Ng-exposed population, 2) define the conservation and distribution of Ng antigens by interrogating our genomic database of Ng, 3) generate lead candidates (exploiting their atomic structures and variation) and produce engineered OMVs which will be characterised by state-of-the-art proteomics, 4) evaluate the immunogenicity and protective efficacy of our candidates in the murine model of Ng infection, and examine cellular and serological responses, and 5) refine and combine antigens to deliver pre-clinical validation for effective Ng vaccines, and derive correlates of protection for this important pathogen.