Vibrio cholerae is a bacterial pathogen which causes the severe acute diarrheal disease cholera. Given that a symptomatic incident of cholera can lead to long term protection, a thorough understanding of the immune response to this pathogen is needed to identify parameters critical to the generation and durability of immunity. To approach this, we utilized a live attenuated cholera vaccine to model the response to V. cholerae infection in 12 naïve subjects. We found that this live attenuated vaccine induced durable vibriocidal antibody titers that were maintained at least one year after vaccination. Similar to what we previously reported in infected patients from Bangladesh, we found that vaccination induced plasmablast responses were primarily specific to the two immunodominant antigens lipopolysaccharide (LPS) and cholera toxin (CT). Interestingly, the magnitude of the early plasmablast response at day 7 predicted the serological outcome of vaccination at day 30. However, this correlation was no longer present at later timepoints. The acute responses displayed preferential immunoglobulin isotype usage, with LPS specific cells being largely IgM or IgA producing, while cholera toxin responses were predominantly IgG. Finally, CCR9 was highly expressed on vaccine induced plasmablasts, especially on IgM and IgA producing cells, suggesting a role in migration to the gastrointestinal tract. Collectively, these findings demonstrate that the use of a live attenuated cholera vaccine is an effective tool to examine the primary and long-term immune response following V. cholerae exposure. Additionally, it provides insight into the phenotype and specificity of the cells which likely return to and mediate immunity at the intestinal mucosa. A thorough understanding of these properties both in peripheral blood and in the intestinal mucosae will inform future vaccine development against both cholera and other mucosal pathogens. Trial Registration: NCT03251495.

中文翻译：

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接种霍乱弧菌减毒活疫苗后人体体液反应的纵向分析。

霍乱弧菌是引起严重急性腹泻病霍乱的细菌病原体。鉴于霍乱的症状性事件可导致长期保护，因此需要彻底了解对该病原体的免疫反应，以确定对免疫的产生和持久性至关重要的参数。为了解决这个问题，我们使用了霍乱减毒活疫苗来模拟 12 名未感染受试者对霍乱弧菌感染的反应。我们发现这种减毒活疫苗诱导了持久的杀弧菌抗体滴度，在接种疫苗后至少保持一年。与我们之前在孟加拉国受感染患者中报告的情况类似，我们发现疫苗接种诱导的浆母细胞反应主要针对两种免疫优势抗原脂多糖 (LPS) 和霍乱毒素 (CT)。有趣的是，第 7 天早期浆母细胞反应的大小预测了第 30 天疫苗接种的血清学结果。然而，这种相关性在以后的时间点不再存在。急性反应显示优先使用免疫球蛋白同种型，LPS 特异性细胞主要产生 IgM 或 IgA，而霍乱毒素反应主要是 IgG。最后，CCR9 在疫苗诱导的浆母细胞上高度表达，尤其是在产生 IgM 和 IgA 的细胞上，表明其在向胃肠道迁移中起作用。总的来说，这些发现表明，使用霍乱减毒活疫苗是检查接触霍乱弧菌后的初级和长期免疫反应的有效工具。此外，它提供了对可能返回并介导肠粘膜免疫的细胞的表型和特异性的深入了解。彻底了解外周血和肠粘膜中的这些特性将为未来针对霍乱和其他粘膜病原体的疫苗开发提供信息。试用注册：NCT03251495。