Neisseria gonorrhoeae (Ng) is the causative agent of gonorrhoea, a sexually transmitted infection that remains a significant concern with ~100 million global cases per annum. There is currently no gonorrhoea vaccine, however, observational studies suggest that the 4CMenB vaccine, licensed to protect against the closely related bacteria Neisseria meningitidis, may provide cross-protection against Ng. We are currently investigating the ability of 4CMenB to protect against Ng in people at high risk of Ng infection in the MenGO randomised control trial. Here, we investigate the antibody response to Ng and the glycosylation profile of these antibodies following 4CMenB vaccination in MenGO participants.
4CMenB contains several antigens, including the Neisseria Heparin-Binding Antigen (NHBA), which is highly conserved in Ng. IgG antibody responses to NHBA in serum from vaccinated and unvaccinated participants were quantified via enzyme-linked immunosorbent assays (ELISAs). We observed a significant increase in the total IgG responses against gonococcal NHBA in the 4CMenB vaccinated group at the 6-month study visit (3 months post dose 2) but not the unvaccinated cohort.
Total IgG and NHBA-specific IgG have also been isolated, using Melon Gel and N-Hydroxysuccinimidyl-Sepharose resin, respectively, to enable analysis of their glycosylation profile by Mass Spectrometry. Total and NHBA-specific IgG1, IgG2, IgG3 and IgG4 isotypes have been detected, with IgG1 being the most abundant isotype. Fucosylation, galactosylation and bisecting N-glycans were observed. Subsequent experiments will further investigate antibody glycosylation on an expanded set of samples.
4CMenB vaccination leads to an increased antibody response to NHBA, which may mediate protection against Ng infection. Future work to investigate specific 4CMenB-induced immune response will help determine the mechanisms of cross-protection against Ng.