Fegan Jamie E, Islam Epshita A, Curran David M, Ng Dixon, Au Natalie Y T, Currie Elissa G, Zeppa Joseph J, Lam Jessica, Schryvers Anthony B, Moraes Trevor F, Gray-Owen Scott D
Department of Molecular Genetics, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada.
Department of Biochemistry, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada.
NPJ Vaccines. 2025 Jan 15;10(1):10. doi: 10.1038/s41541-024-01054-0.
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.
淋病奈瑟菌仍是一个持续存在的公共卫生问题，部分原因是开发有效的预防性传播感染疫苗的努力未取得成功。淋球菌转铁蛋白结合蛋白B（TbpB）是一种有吸引力的候选疫苗抗原。然而，它表现出高水平的抗原变异性，这在引发广泛保护性免疫反应方面构成了重大障碍。在这里，我们利用系统发育信息合理选择TbpB变体纳入淋球菌疫苗，并鉴定出两种TbpB变体，它们共同引发针对多种TbpB变体和临床相关淋球菌菌株的高度交叉反应性抗体反应。这种制剂在实际使用的实验模型中表现良好，包括对多种淋球菌菌株产生杀菌活性，并缩短雌性小鼠阴道感染后定植的中位持续时间。这些数据支持使用TbpB变体组合来制备具有广泛保护作用的淋球菌疫苗。
