Department of Microbiology, and Department of Dermatology of Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Emerg Microbes Infect. 2023 Dec;12(2):2249124. doi: 10.1080/22221751.2023.2249124.
Global dissemination of high-level ceftriaxone-resistant strains associated with the FC428 clone poses a threat to the efficacy ceftriaxone-based therapies. Vaccination is the best strategy to contain multidrug-resistant infections. In this study, we investigated the efficacy of MtrE and its surface Loop2 as vaccine antigens when combined with a Th1-polarizing adjuvant, which is expected to be beneficial for gonococcal vaccine development. Using in vitro dendritic cell maturation and T cell differentiation assays, CpG1826 was identified as the optimal Th1-polarizing adjuvant for MtrE and Loop2 displayed as linear epitope (Nloop2) or structural epitope (Intraloop2) on a carrier protein. Loop2-based antigens raised strongly Th1-polarized and bactericidal antibody responses in vaccinated mice. Furthermore, the vaccine formulations provided protection against a gonococcal challenge in mouse vaginal tract infection model when provided as prophylactic vaccines. Also, the vaccine formulations accelerated gonococcal clearance when provided as a single therapeutic dose to treat an already established infection, including against a strain associated with the FC428 clone. Therefore, this study demonstrated that MtrE and Loop 2 are effective gonococcal vaccine antigens when combined with the Th1-polarizing CpG1826 adjuvant.
全球高水平头孢曲松耐药株的传播与 FC428 克隆有关，这对基于头孢曲松的治疗效果构成了威胁。疫苗接种是控制多药耐药感染的最佳策略。在这项研究中，我们研究了 MtrE 及其表面环 2 作为疫苗抗原与 Th1 极化佐剂联合使用的效果，这有望有益于淋病奈瑟菌疫苗的开发。通过体外树突状细胞成熟和 T 细胞分化试验，CpG1826 被鉴定为 MtrE 的最佳 Th1 极化佐剂，而环 2 作为线性表位（Nloop2）或结构表位（Intraloop2）在载体蛋白上显示。基于环 2 的抗原在接种小鼠中引起强烈的 Th1 极化和杀菌抗体反应。此外，当作为预防性疫苗使用时，疫苗制剂在小鼠阴道感染模型中提供了针对淋病奈瑟菌挑战的保护。此外，当作为单一治疗剂量用于治疗已建立的感染时，疫苗制剂也加速了淋病奈瑟菌的清除，包括针对与 FC428 克隆相关的菌株。因此，这项研究表明，MtrE 和环 2 与 Th1 极化的 CpG1826 佐剂联合使用时，是有效的淋病奈瑟菌疫苗抗原。
