Laboratory of Bacterial Polysaccharides, Division of Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
J Infect Dis. 2022 Feb 15;225(4):650-660. doi: 10.1093/infdis/jiab450.
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.
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.
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.
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.
尽管经过了几十年的研究努力，淋病疫苗的开发仍然难以实现。流行病学研究表明，脑膜炎奈瑟菌（Nm）的脱毒外膜囊泡（dOMV）疫苗可能对预防淋病奈瑟菌（Ng）感染有保护作用。我们最近报告称，缺乏主要外膜蛋白（OMPs）PorA、PorB 和 RmpM 的 Nm dOMV 比野生型（WT）dOMV 引起更大的针对异源 Nm 菌株的抗体交叉反应性，并且可能代表一种针对淋病的改良疫苗。
我们从 PorA、PorB 和 RmpM 充足或缺失的脑膜炎奈瑟菌株中制备了 dOMV 疫苗。在小鼠生殖道感染模型中测试了疫苗，并用抗血清鉴定了疫苗靶点。
用 OMP 缺陷 dOMV 免疫的小鼠中，Nm dOMV 免疫显著且可重复地增强了淋球菌的清除率；在两项实验中的一项中，观察到 WT dOMV 免疫的小鼠有明显的清除率。清除率与血清和阴道抗 Nm dOMV 免疫球蛋白 G（IgG）抗体有关，这些抗体与 Ng 发生交叉反应。血清 IgG 用于鉴定潜在的 Ng 疫苗靶点，包括 PilQ、MtrE、NlpD 和 GuaB。
脑膜炎奈瑟菌 dOMV 引起了对实验性淋病奈瑟菌感染的保护作用。Nm dOMV 诱导的抗体对 Ng 疫苗靶点的识别和鉴定支持开发交叉保护的奈瑟氏菌疫苗。
