Neisseria gonorrhoeae, which causes the sexually transmitted infection gonorrhoea, is a major public health problem worldwide with an estimated global incidence of 106 million cases/year. If left untreated, gonorrhoea can lead to severe sequelae such as pelvic inflammatory disease, neonatal complications, infertility, and an increased risk of HIV. Due to the emergence of multi-drug resistant gonococcal strains, gonorrhoea is recognised by WHO and CDC as an urgent threat to global health. There is currently no vaccine, and no new antibiotics or vaccine candidates in late-stage development.
To facilitate gonococcal vaccine development, we performed mathematical modelling to predict the impact of different vaccine scenarios. This modelling indicates that even a modestly efficacious vaccine could have a substantial impact on gonorrhoea prevalence and sequelae. We have also characterised two highly conserved and immunogenic candidate vaccine antigens. In vitro assays, using wild type, knock-out and complemented strains, have shown that NGO1958 (gonococcal homologue of the Neisseria heparin binding antigen (NHBA) that is present in the serogroup B meningococcal vaccine Bexsero) is involved in serum resistance and adherence to cervical epithelial cells. Similar assays show that NGO2139 (a methionine uptake receptor, MetQ) is involved in resistance to killing by human serum, monocytes and macrophages, as well as adherence and invasion of cervical epithelial cells. Antibodies to these proteins mediate complement-dependent killing and can reduce gonococcal infection of cervical epithelial cells.
In summary, we have characterised two recombinant protein antigens that elicit both bactericidal and functional blocking antibodies, which are valid candidate antigens for possible inclusion in an urgently needed vaccine for the prevention of gonorrhea.