Neisseria gonorrhoeae (Gc) is an obligate human pathogen and the causative agent of the sexually transmitted infection gonorrhoea. There are over 106 million reported cases of gonorrhoea each year worldwide, however the actual number of infections is difficult to estimate due to high incidence of asymptomatic infections (up to 40% in men and 50-80% in women). Undiagnosed and/or untreated gonococcal infections can progress to severe sequelae, such as pelvic inflammatory disease (PID) in women, which can lead to infertility. In addition, infections with Gc also facilitate transmission of HIV. The Wold Health Organisation and Centres for Decease Control have both declared N. gonorrhoeae as an urgent threat to global health, due to increasing incidence and widespread antibiotic resistance. Development of a gonococcal vaccine has been challenging, as the bacterium is known for its high rate of antigenic variation as well as its ability to suppress protective immunity (i.e., natural infection with Gc offers no protection against subsequent re-infection). Therefore, vaccine development requires identification of suitable candidates that can induce a non-native, protective immune response.
We have characterised several minor components of the gonococcal outer membrane and investigated their potential use as vaccine antigens. Here we discuss two antigens, MetQ (methionine receptor) and NHBA (Neisseria heparin binding antigen), that were identified as potential vaccine targets using a reverse vaccinology approach. In N. gonorrhoeae, both of these proteins are surface exposed, immunogenic, highly conserved with minimal amino acid variation between strains, and stably expressed with no evidence of phase variation. Mutant strains lacking MetQ or NBHA have decreased adherence and invasion of cervical and urethral epithelial cells, as well as reduced survival in human serum, highlighting the importance of these surface molecules for gonococcal pathogenesis. Both anti-MetQ and anti-NHBA antibodies from mice elicit complement dependent bactericidal activity, and anti-NHBA antibodies also facilitate opsonophagocytic killing of Gc. NHBA from the closely related bacteria Neisseria meningitidis is present in the licensed multicomponent meningococcal serogroup B vaccine Bexsero, and we have determined that Bexsero induces antibodies in humans that recognise the gonococcal NHBA homologue. Work is ongoing to identify the full set of gonococcal targets recognized by Bexsero-induced antibodies, and their functional activity against gonorrhoea.