Rational selection of TbpB variants yields a bivalent vaccine with broad coverage against Neisseria gonorrhoeae

Abstract Neisseria gonorrhoeae is an on-going public health problem due in part to the lack of success with efforts to develop an efficacious vaccine to prevent this sexually transmitted infection. The gonococcal transferrin binding protein B (TbpB) is an attractive candidate vaccine antigen. Howeve...

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Main Authors: Jamie E. Fegan, Epshita A. Islam, David M. Curran, Dixon Ng, Natalie Y. T. Au, Elissa G. Currie, Joseph J. Zeppa, Jessica Lam, Anthony B. Schryvers, Trevor F. Moraes, Scott D. Gray-Owen
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:npj Vaccines
Online Access:https://doi.org/10.1038/s41541-024-01054-0
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Summary:Abstract Neisseria gonorrhoeae is an on-going public health problem due in part to the lack of success with efforts to develop an efficacious vaccine to prevent this sexually transmitted infection. The gonococcal transferrin binding protein B (TbpB) is an attractive candidate vaccine antigen. However, it exhibits high levels of antigenic variability, posing a significant obstacle in evoking a broadly protective immune response. Here, we utilize phylogenetic information to rationally select TbpB variants for inclusion into a gonococcal vaccine and identify two TbpB variants that together elicit a highly cross-reactive antibody response against a diverse panel of TbpB variants and clinically relevant gonococcal strains. This formulation performed well in experimental proxies of real-world usage, including eliciting bactericidal activity against diverse gonococcal strains and decreasing the median duration of colonization after vaginal infection in female mice. These data support the use of a combination of TbpB variants for a broadly protective gonococcal vaccine.
ISSN:2059-0105