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Experimental Vaccine Induces Th1-driven Immune Responses and Resistance to Neisseria gonorrhoeae Infection in a Murine Model

机译:实验性疫苗在小鼠模型中诱导Th1驱动的免疫反应和对淋病奈瑟菌的抗性。

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摘要

Female mice were immunized intravaginally with gonococcal outer membrane vesicles (OMV) plus microencapsulated IL-12, and challenged using an established model of genital infection with Neisseria gonorrhoeae. Whereas sham-immunized and control animals cleared the infection in 10–13 days, those immunized with OMV plus IL-12 cleared infection with homologous gonococcal strains in 6–9 days. Significant protection was also seen after challenge with antigenically distinct strains of N. gonorrhoeae, and protective anamnestic immunity persisted for at least 6 months after immunization. Serum and vaginal IgG and IgA antibodies were generated against antigens expressed by homologous and heterologous strains. Iliac lymph node CD4+ T cells secreted IFNγ, but not IL-4, in response to immunization, and produced IL-17 in response to challenge regardless of immunization. Antigens recognized by immunized mouse serum included several shared between gonococcal strains, including two identified by immunoproteomics approaches as EF-Tu and PotF3. Experiments with immunodeficient mice showed that protective immunity depended upon IFNγ and B cells, presumably to generate antibodies. The results demonstrated that immunity to gonococcal infection can be induced by immunization with a non-living gonococcal antigen, and suggest that efforts to develop a human vaccine should focus on strategies to generate Th1-driven immune responses in the genital tract.
机译:用淋球菌外膜囊泡(OMV)和微囊化的IL-12阴道内免疫雌性小鼠,并使用已建立的淋病奈瑟菌生殖器感染模型进行攻击。假免疫和对照动物在10-13天内清除了感染,而用OMV和IL-12免疫的动物在6-9天内清除了同源淋球菌菌株的感染。用淋病奈瑟氏球菌的抗原性不同的菌株攻击后也看到了显着的保护作用,并且保护性记忆消除免疫在免疫后至少持续了6个月。产生针对由同源和异源菌株表达的抗原的血清和阴道IgG和IgA抗体。免疫反应后,node淋巴结CD4 + T细胞分泌IFNγ,但不分泌IL-4,无论免疫反应如何,IL-6均可激发攻击。免疫小鼠血清识别的抗原包括淋球菌菌株之间共享的几种抗原,包括通过免疫蛋白质组学方法鉴定的两种抗原,如EF-Tu和PotF3。免疫缺陷小鼠的实验表明,保护性免疫依赖于IFNγ和B细胞,大概是产生抗体。结果表明对非淋球菌抗原的免疫可以诱导对淋球菌感染的免疫力,并表明开发人类疫苗的努力应侧重于在生殖道中产生Th1驱动的免疫应答的策略。

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