Meningococcal vaccine 4CMenB elicits a robust cellular immune response that targets but is not consistently protective against Neisseria gonorrhoeae during murine vaginal infection.

IF 3.7 2区 生物学 Q2 MICROBIOLOGY
mSphere Pub Date : 2025-05-27 Epub Date: 2025-04-16 DOI:10.1128/msphere.00940-24
Joseph J Zeppa, Jamie E Fegan, Pauline Maiello, Epshita A Islam, Isaac S Lee, Christine Pham, Laura-Lee Caruso, Scott D Gray-Owen
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Abstract

Retrospective epidemiological studies suggest that the licensed serogroup B meningococcal vaccine 4CMenB (Bexsero) provides some protection against the closely related pathogen Neisseria gonorrhoeae in humans. This result has been replicated in murine models of gonococcal colonization, with a gonococci-reactive humoral response and more rapid clearance of vaginal infection. However, immunization with 4CMenB consistently elicits a robust humoral response but does not protect all individuals; hence, the correlates of protection remain undefined. Herein, we exploit the fact that 4CMenB promotes gonococcal clearance in only a subset of immunized mice to perform a broad analysis of the adaptive response in animals that are or are not protected. We observe that 4CMenB vaccination induces high levels of anti-neisserial antibodies in both serum and the vaginal lumen, and a robust cellular response highlighted by an increase in both conventional naïve and memory populations as well as unconventional lymphocyte subsets. Multiplex and flow cytometry results show that 4CMenB vaccination generates a robust, multi-faceted cytokine response that spans numerous T cell subsets (TH1, TH2, Treg, and TH17) and that non-T non-B lymphocytes play an important role in this response, as indicated by an unbiased principal component analysis. Together, this work provides the first comprehensive analysis of the robust humoral and complex cellular response to 4CMenB so as to reveal the effector mechanisms that may contribute to immunity against vaginal gonococcal infection.IMPORTANCEGonorrhea, a sexually transmitted infection caused by the human-specific pathogen Neisseria gonorrhoeae (Ngo), is a growing public health concern due to its rise in prevalence and increasing antibiotic resistance against first-line agents. There is currently no vaccine available for this important bacterium due, in part, to our lack of understanding of immune correlates of protection. Interestingly, a human-approved vaccine (4CMenB; Bexsero) against a related pathogen (N. meningitidis; a cause of meningitis) has demonstrated some protection against gonorrhea in epidemiologic studies. Herein, we provide the first detailed analysis of cellular and antibody-mediated immune responses to this vaccine in animals protected against gonococcal colonization. These findings provide new understanding regarding immune correlates of protection against N. gonorrhoeae, providing new insight into immune protection and helping guide the development of a much-needed vaccine.

在小鼠阴道感染期间,脑膜炎球菌疫苗4CMenB引发了一种强大的细胞免疫反应,其目标是淋病奈瑟菌,但并不始终具有保护作用。
回顾性流行病学研究表明,已获得许可的血清B群脑膜炎球菌疫苗4CMenB (Bexsero)对人类密切相关的淋病奈瑟菌病原体具有一定的保护作用。这一结果在淋球菌定植的小鼠模型中得到了重复,具有淋球菌反应性体液反应和更快的阴道感染清除。然而,4CMenB免疫始终引起强烈的体液反应,但并不能保护所有个体;因此,保护的相关关系仍然不明确。在此,我们利用4CMenB仅在一小部分免疫小鼠中促进淋球菌清除的事实,对受到或未受到保护的动物的适应性反应进行了广泛的分析。我们观察到,4CMenB疫苗接种在血清和阴道腔中诱导高水平的抗奈瑟氏球菌抗体,并且通过增加传统naïve和记忆群体以及非常规淋巴细胞亚群来突出显示强大的细胞反应。多重和流式细胞术结果显示,4CMenB疫苗接种产生强大的,多方面的细胞因子反应,跨越多个T细胞亚群(TH1, TH2, Treg和TH17),非T -非b淋巴细胞在这种反应中起重要作用,无偏主成分分析表明。总之,这项工作首次全面分析了对4CMenB的强大的体液和复杂的细胞反应,从而揭示了可能有助于免疫阴道淋球菌感染的效应机制。淋病是一种由人类特有的淋病奈瑟菌(Ngo)引起的性传播感染,由于其患病率上升和对一线药物的抗生素耐药性增加而日益引起公共卫生关注。目前还没有针对这种重要细菌的疫苗,部分原因是我们对保护的免疫相关因素缺乏了解。有趣的是,一种人类批准的疫苗(4CMenB;Bexsero)对抗相关病原体(脑膜炎奈瑟菌;流行病学研究表明,淋病(脑膜炎的一种病因)对淋病有一定的保护作用。在此,我们提供了细胞和抗体介导的免疫反应的第一个详细的分析,这种疫苗在动物保护免受淋球菌定植。这些发现提供了对淋病奈瑟菌保护的免疫相关的新认识,为免疫保护提供了新的见解,并有助于指导急需的疫苗的开发。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
mSphere
mSphere Immunology and Microbiology-Microbiology
CiteScore
8.50
自引率
2.10%
发文量
192
审稿时长
11 weeks
期刊介绍: mSphere™ is a multi-disciplinary open-access journal that will focus on rapid publication of fundamental contributions to our understanding of microbiology. Its scope will reflect the immense range of fields within the microbial sciences, creating new opportunities for researchers to share findings that are transforming our understanding of human health and disease, ecosystems, neuroscience, agriculture, energy production, climate change, evolution, biogeochemical cycling, and food and drug production. Submissions will be encouraged of all high-quality work that makes fundamental contributions to our understanding of microbiology. mSphere™ will provide streamlined decisions, while carrying on ASM''s tradition for rigorous peer review.
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