Introduction Neisseria gonorrhoeae, the causative agent gonorrhoea, is a major public health problem worldwide with an estimated global incidence of 106 million cases/yr. If left undiagnosed or untreated, infection can lead to severe sequelae that include pelvic inflammatory disease, infertility, neonatal complications, and an increased risk of HIV. It recognised by WHO and CDC as an urgent threat to global health due to the emergence of multi-drug resistant gonococcal strains. There is currently no vaccine, and no new antibiotics or new vaccine candidates in late-stage development.
Methods To facilitate gonococcal vaccine development, we performed mathematical modelling to predict the impact of different vaccine scenarios. We have also identified and characterised a series of potential vaccine candidates.
Results Mathematical modelling of different vaccine scenarios indicates that even a modestly efficacious vaccine could have a substantial impact on gonorrhoea prevalence and sequelae. We have also characterised 2 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) present in the serogroup B meningococcal vaccine) is involved in serum resistance and adherence to cervical epithelial cells. Similar assays show that NGO2139 (methionine uptake receptor) 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 are bactericidal and can block gonococcal infection of cervical epithelial cells. Additional studies are underway to determine if antibodies to these proteins can protect again infection in a mouse model.
Conclusion We present two 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 gonorrhoea.
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