Meningococcal vaccine Bexsero elicits a robust cellular immune response that targets but is not consistently protective against Neisseria gonorrhoeae during murine vaginal infection
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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引用次数: 0
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 Bexsero consistently elicits a robust humoral response but does not protect all individuals, so the correlates of protection remain undefined. Herein, we exploit the fact that Bexsero promotes 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 Bexsero 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 naive and memory populations as well as unconventional lymphocyte subsets. Multiplex and flow cytometry results show that Bexsero vaccination generates a robust, multi-faceted cytokine response that spans numerous T cell subsets (TH1, TH2, Treg and TH17 responses) 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 Bexsero so as to reveal the effector mechanisms that may contribute to immunity against vaginal gonococcal infection.
回顾性流行病学研究表明,获得许可的血清 B 群脑膜炎球菌疫苗 4CMenB(Bexsero)对人类密切相关的病原体淋病奈瑟菌有一定的保护作用。这一结果在淋球菌定植的小鼠模型中得到了复制,出现了淋球菌反应性体液反应,阴道感染清除得更快。然而,用 Bexsero 免疫接种可持续引起强大的体液反应,但并不能保护所有个体,因此保护的相关因素仍未确定。在本文中,我们利用 Bexsero 只对免疫小鼠中的一部分产生清除作用这一事实,对受到或未受到保护的动物的适应性反应进行了广泛分析。我们观察到,Bexsero 疫苗接种能在血清和阴道腔中诱导出高水平的抗奈瑟氏菌抗体,并诱导出强大的细胞反应,突出表现为传统的幼稚群和记忆群以及非常规淋巴细胞亚群的增加。多重和流式细胞术结果表明,Bexsero 疫苗接种会产生强大的、多方面的细胞因子反应,跨越多个 T 细胞亚群(TH1、TH2、Treg 和 TH17 反应),而且非 T 非 B 淋巴细胞在这种反应中发挥了重要作用,无偏主成分分析表明了这一点。总之,这项研究首次全面分析了对贝克斯罗的强大体液和复杂细胞反应,从而揭示了可能有助于抵抗阴道淋球菌感染的效应机制。