Genetic Similarity of Gonococcal Homologs to Meningococcal Outer Membrane Proteins of Serogroup B Vaccine

Abstract

The human pathogens Neisseria gonorrhoeae and Neisseria meningitidis share high genome identity. Retrospective analysis of surveillance data from New Zealand indicates the potential cross-protective effect of outer membrane vesicle (OMV) meningococcal serogroup B vaccine (MeNZB) against N. gonorrhoeae. A licensed OMV-based MenB vaccine, MenB-4C, consists of a recombinant FHbp, NhbA, NadA, and the MeNZB OMV. Previous work has identified several abundantly expressed outer membrane proteins (OMPs) as major components of the MenB-4C OMV with high sequence similarity between N. gonorrhoeae and N. meningitidis, suggesting a mechanism for cross-protection. To build off these findings, we performed comparative genomic analysis on 970 recent N. gonorrhoeae isolates collected through a U.S surveillance system against N. meningitidis serogroup B (NmB) reference sequences. We identified 1,525 proteins that were common to both Neisseria species, of which 57 proteins were predicted to be OMPs using in silico methods. Among the MenB-4C antigens, NhbA showed moderate sequence identity (73%) to the respective gonococcal homolog, was highly conserved within N. gonorrhoeae, and was predicted to be surface expressed. In contrast, the gonococcal FHbp was predicted not to be surface expressed, while NadA was absent in all N. gonorrhoeae isolates. Our work confirmed recent observations (E. A. Semchenko, A. Tan, R. Borrow, and K. L. Seib, Clin Infect Dis, 2018, https://doi.org/10.1093/cid/ciy1061) and describes homologous OMPs from a large panel of epidemiologically relevant N. gonorrhoeae strains in the United States against NmB reference strains. Based on our results, we report a set of OMPs that may contribute to the previously observed cross-protection and provide potential antigen targets to guide the next steps in gonorrhea vaccine development. IMPORTANCE Gonorrhea, a sexually transmitted disease, causes substantial global morbidity and economic burden. New prevention and control measures for this disease are urgently needed, as strains resistant to almost all classes of antibiotics available for treatment have emerged. Previous reports demonstrate that cross-protection from gonococcal infections may be conferred by meningococcal serogroup B (MenB) outer membrane vesicle (OMV)-based vaccines. Among 1,525 common proteins shared across the genomes of both N. gonorrhoeae and N. meningitidis, 57 proteins were predicted to be surface expressed (outer membrane proteins [OMPs]) and thus preferred targets for vaccine development. The majority of these OMPs showed high sequence identity between the 2 bacterial species. Our results provide valuable insight into the meningococcal antigens present in the current OMV-containing MenB-4C vaccine that may contribute to cross-protection against gonorrhea and may inform next steps in gonorrhea vaccine development.

A community-driven resource for genomic epidemiology and antimicrobial resistance prediction of Neisseria gonorrhoeae at Pathogenwatch

“…Plasmid and tetM/blaTEM subtyping as recently described [147] will also be considered within the development roadmap of Pathogenwatch. Including a separate library to automatically screen targets of potential interest for vaccine design [148][149][150] as well as targets of new antibiotics currently in phase III clinical trials (i.e. zoliflodacin [151] or gepotidacin [152]) can also be an interesting addition to the scheme.…”

Looking beyond meningococcal B with the 4CMenB vaccine: the Neisseria effect

“…Immunization with 4CMenB may provide protection against non-B meningococcal serogroups and gonococcal strains that contain one or more 4CMenB antigen genes or express vaccine antigens with close similarity and enough density 24 , 28 – 30 .…”

“…For N. gonorrhoeae , no effective vaccine has been developed yet, but there is increasing evidence that the 4CMenB vaccine may help protect against infection with gonococcal strains 28 – 30 . This is also the case for non-B meningococcal strains as most of them express the vaccine antigens 24 , 31 .…”

A community-driven resource for genomic epidemiology and antimicrobial resistance prediction ofNeisseria gonorrhoeaeat Pathogenwatch

“…Including a separate library to automatically screen targets of potential interest for vaccine design (148)(149)(150) as well as targets of new antibiotics currently in phase III clinical trials (i.e. zoliflodacin (151) or gepotidacin (152)) can also be an interesting addition to the scheme.…”