The Serogroup B Meningococcal Vaccine Bexsero Elicits Antibodies to Neisseria gonorrhoeae

Abstract

Background Neisseria gonorrhoeae and Neisseria meningitidis are closely-related bacteria that cause a significant global burden of disease. Control of gonorrhoea is becoming increasingly difficult, due to widespread antibiotic resistance. While vaccines are routinely used for N. meningitidis, no vaccine is available for N. gonorrhoeae. Recently, the outer membrane vesicle (OMV) meningococcal B vaccine, MeNZB, was reported to be associated with reduced rates of gonorrhoea following a mass vaccination campaign in New Zealand. To probe the basis for this protection, we assessed the cross-reactivity to N. gonorrhoeae of serum raised to the meningococcal vaccine Bexsero, which contains the MeNZB OMV component plus 3 recombinant antigens (Neisseria adhesin A, factor H binding protein [fHbp]-GNA2091, and Neisserial heparin binding antigen [NHBA]-GNA1030). Methods A bioinformatic analysis was performed to assess the similarity of MeNZB OMV and Bexsero antigens to gonococcal proteins. Rabbits were immunized with the OMV component or the 3 recombinant antigens of Bexsero, and Western blots and enzyme-linked immunosorbent assays were used to assess the generation of antibodies recognizing N. gonorrhoeae. Serum from humans immunized with Bexsero was investigated to assess the nature of the anti-gonococcal response. Results There is a high level of sequence identity between MeNZB OMV and Bexsero OMV antigens, and between the antigens and gonococcal proteins. NHBA is the only Bexsero recombinant antigen that is conserved and surfaced exposed in N. gonorrhoeae. Bexsero induces antibodies in humans that recognize gonococcal proteins. Conclusions The anti-gonococcal antibodies induced by MeNZB-like OMV proteins could explain the previously-seen decrease in gonorrhoea following MeNZB vaccination. The high level of human anti-gonococcal NHBA antibodies generated by Bexsero vaccination may provide additional cross-protection against gonorrhoea.

Potential benefits of using a multicomponent vaccine for prevention of serogroup B meningococcal disease

“…A retrospective case-control study estimated a vaccine effectiveness of 31% in preventing gonorrhea infection among fully vaccinated 15-30-year-olds (Petousis-Harris et al, 2017), showing the potential of OMV vaccines to reduce the incidence of gonorrhea. In addition, other non-OMV components of 4CMenB could further contribute to cross-protection, in particular NHBA, which is highly conserved across gonococcal strains (Comanducci et al, 2002;Hadad et al, 2012;Semchenko et al, 2018). Given growing concerns relating to gonococcal infections and the threat of antimicrobial resistance, any disease reduction attributable to 4CMenB use would be highly desirable from a public health perspective.…”

Factors that influence Neisseria gonorrhoeae antimicrobial resistance and transmission in Australia

“…The current Bexsero N. meningitidis serogroup B vaccine contains recombinant proteins which may provide additional cross-protection for N. gonorrhoeae, particularly the NHBA peptide which is the only one known to be surface exposed (238). Our results show that there were several NHBA peptides found in the top 10 N. gonorrhoeae strains in Australia.…”

“…Although that particular vaccine is no longer available, the vaccine components are included in the current Bexsero vaccine which also contains additional recombinant proteins including NHBA, factor H binding protein (fHbp) and Neisseria adhesion A (NadA) (251). Of these, NHBA appears to be the only one which is surface exposed, making a viable target for vaccine efficacy (238). Semchenko et al (238) showed that NHBA is well conserved among N. gonorrhoeae and that three NHBA variants (475, 481 and 542), which were also found in our top 10, account for a large majority of N. gonorrhoeae isolates found in the pubMLST database and noted cross-reactivity for NHBA in both N. gonorrhoeae and N.…”

“…Of these, NHBA appears to be the only one which is surface exposed, making a viable target for vaccine efficacy (238). Semchenko et al (238) showed that NHBA is well conserved among N. gonorrhoeae and that three NHBA variants (475, 481 and 542), which were also found in our top 10, account for a large majority of N. gonorrhoeae isolates found in the pubMLST database and noted cross-reactivity for NHBA in both N. gonorrhoeae and N.…”

“…Other fitness markers of interest include the DNA methyltransferase genes modA and modB that act as epigenetic regulators for N. gonorrhoeae (236), as well as specific compensatory mutations found in acnB and mleN (135). to be surface exposed in addition to inducing anti-gonococcal antibodies, potentially highlighting additional cross-protection for gonorrhoea (238). Therefore, NHBA was investigated using pubMLST (158) to determine similarity towards the NHBA peptide found in the N. meningitidis serogroup B Bexsero vaccine.…”