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<p><i>Neisseria gonorrhoeae</i> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月15日

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  • 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

摘要

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.