Background Despite decades of research efforts, development of a gonorrhea vaccine has remained elusive. Epidemiological studies suggest that detoxified outer membrane vesicle (dOMV) vaccines from Neisseria meningitidis (Nm) may protect against infection with Neisseria gonorrhoeae (Ng). We recently reported that Nm dOMVs lacking the major outer membrane proteins (OMPs) PorA, PorB, and RmpM induced greater antibody cross-reactivity against heterologous Nm strains than wild-type (WT) dOMVs and may represent an improved vaccine against gonorrhea. Methods We prepared dOMV vaccines from meningococcal strains that were sufficient or deleted for PorA, PorB, and RmpM. Vaccines were tested in a murine genital tract infection model and antisera were used to identify vaccine targets. Results Immunization with Nm dOMVs significantly and reproducibly enhanced gonococcal clearance for mice immunized with OMP-deficient dOMVs; significant clearance for WT dOMV-immunized mice was observed in one of two experiments. Clearance was associated with serum and vaginal anti-Nm dOMV immunoglobulin G (IgG) antibodies that cross-reacted with Ng. Serum IgG was used to identify putative Ng vaccine targets, including PilQ, MtrE, NlpD, and GuaB. Conclusions Meningococcal dOMVs elicited a protective effect against experimental gonococcal infection. Recognition and identification of Ng vaccine targets by Nm dOMV-induced antibodies supports the development of a cross-protective Neisseria vaccine.

中文翻译：

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脑膜炎球菌解毒外膜囊泡疫苗可增强鼠感染模型中淋球菌的清除率

背景 尽管经过数十年的研究努力，淋病疫苗的开发仍然难以捉摸。流行病学研究表明，来自脑膜炎奈瑟菌 (Nm) 的解毒外膜囊泡 (dOMV) 疫苗可预防淋病奈瑟菌 (Ng) 感染。我们最近报道，与野生型 (WT) dOMV 相比，缺乏主要外膜蛋白 (OMP) PorA、PorB 和 RmpM 的 Nm dOMV 对异源 Nm 菌株的抗体交叉反应性更强，这可能代表了一种改进的淋病疫苗。方法 我们从对 PorA、PorB 和 RmpM 足够或缺失的脑膜炎球菌菌株制备 dOMV 疫苗。疫苗在鼠生殖道感染模型中进行了测试，并使用抗血清来识别疫苗靶标。结果 Nm dOMV 免疫显着和可重复地增强了用 OMP 缺陷 dOMV 免疫的小鼠的淋球菌清除率；在两个实验之一中观察到 WT dOMV 免疫小鼠的显着清除。清除率与血清和阴道抗-Nm dOMV 免疫球蛋白 G (IgG) 抗体相关，后者与 Ng 发生交叉反应。血清 IgG 用于鉴定推定的 Ng 疫苗靶标，包括 PilQ、MtrE、NlpD 和 GuaB。结论 脑膜炎球菌 dOMV 对实验性淋球菌感染具有保护作用。Nm dOMV 诱导的抗体对 Ng 疫苗靶点的识别和鉴定支持了交叉保护奈瑟菌疫苗的开发。清除率与血清和阴道抗-Nm dOMV 免疫球蛋白 G (IgG) 抗体相关，后者与 Ng 发生交叉反应。血清 IgG 用于鉴定推定的 Ng 疫苗靶标，包括 PilQ、MtrE、NlpD 和 GuaB。结论 脑膜炎球菌 dOMV 对实验性淋球菌感染具有保护作用。Nm dOMV 诱导的抗体对 Ng 疫苗靶点的识别和鉴定支持了交叉保护奈瑟菌疫苗的开发。清除率与血清和阴道抗-Nm dOMV 免疫球蛋白 G (IgG) 抗体相关，后者与 Ng 发生交叉反应。血清 IgG 用于鉴定推定的 Ng 疫苗靶标，包括 PilQ、MtrE、NlpD 和 GuaB。结论 脑膜炎球菌 dOMV 对实验性淋球菌感染具有保护作用。Nm dOMV 诱导的抗体对 Ng 疫苗靶点的识别和鉴定支持了交叉保护奈瑟菌疫苗的开发。