A WHO report on global antibiotic resistance has listed Neisseria gonorrhoeae as one of the top three ‘urgent’ threats, due to its increasing incidence and widespread resistance to a range of antibiotics, including third-generation cephalosporins. This highlights the need for the development of alternative treatment options and vaccines for N. gonorrhoeae.
This study focuses on functional characterisation of the gonococcal Neisseria heparin binding antigen (NHBA), with an emphasis on its potential use as a vaccine antigen. NHBA of the closely related bacteria, Neisseria meningitidis, is a highly conserved, surface exposed lipoprotein that was named for its ability to bind heparin. This interaction has been linked to protection against serum-mediated killing, though the exact mechanism for this action is not fully characterised. Furthermore, NHBA is one of four protein components in a new meningococcal serogroup B vaccine (Bexsero), and the only one that is present/surface exposed in N. gonorrhoeae. NHBA of the pathogenic Neisseria are highly similar, suggesting that NHBA may also be a potential vaccine target for N. gonorrhoeae.
Localisation studies, with trypsin treated bacteria, have confirmed that the gonococcal NHBA is surface exposed. In vitro assays have also shown that gonococcal NHBA is involved in protection from serum-mediated killing, possibly due to heparin binding, which was confirmed by glycan array analysis. Furthermore, gonococcal NHBA was shown to act as an adhesin, with a nhba knockout strain having decreased adherence to cervical epithelial cells when compared to the wild type strain. Additional studies are underway to determine if anti-NHBA antibodies can prevent gonococcal adherence/invasion of cervical epithelial cells in in vitro cell culture assays. In conclusion, the gonococcal NHBA retains main attributes of its homologue in N. meningitidis and is a promising candidate for a gonococcal vaccine.