Longitudinal analysis of human humoral responses after vaccination with a live attenuated V. cholerae vaccine.
Longitudinal analysis of human humoral responses after vaccination with a live attenuated V. cholerae vaccine.
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DOI：
10.1371/journal.pntd.0009743
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发表时间：
2021-09
影响因子：
3.8
通讯作者：
Wrammert J
中科院分区：
文献类型：
--
作者：
Adekunle O;Dretler A;Kauffman RC;Cho A;Rouphael N;Wrammert J
霍乱弧菌是一种引起严重的急性霍乱的细菌病原体。鉴于霍乱的症状性事件可以导致长期保护，需要彻底了解对这种病原体的免疫反应，以确定对免疫力的产生和持久性至关重要的参数。为了解决这一问题，我们利用减毒活霍乱疫苗来模拟12名初治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持久的杀弧菌抗体滴度，并在接种后至少维持一年。与我们先前在孟加拉国感染患者中报道的相似，我们发现疫苗接种诱导的浆母细胞应答主要特异于两种免疫显性抗原脂多糖（LPS）和霍乱毒素（CT）。有趣的是，第7天早期浆母细胞应答的幅度预测了第30天疫苗接种的血清学结果。然而，在随后的时间点，这种相关性不再存在。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或伊加，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，特别是在IgM和伊加产生细胞上，表明在向胃肠道的迁移中起作用。总的来说，这些研究结果表明，使用减毒活霍乱疫苗是一种有效的工具，以检查主要和长期的免疫反应后，霍乱弧菌暴露。此外，它提供了对细胞的表型和特异性的洞察，这些细胞可能返回并介导肠粘膜的免疫。对外周血和肠粘膜中这些特性的深入了解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。试验注册：NCT 03251495。霍乱是一种严重的传染病，每年影响数百万人。受影响最严重的人居住在发展中国家，在那里爆发可能导致毁灭性的医疗危机。尽管如此，关于保护性免疫反应的寿命或它们是如何产生和维持的，仍然有很多未知数。这包括诱导免疫的粘膜反应的方面，以及可以预测长期免疫的早期免疫反应的特征。为了解决这些问题，我们研究了原发性体液免疫应答后，减毒活霍乱疫苗给12人参与者。这项研究提供了深入了解体液免疫的发展和信息，可能证明有价值的改进霍乱疫苗和治疗。
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. Cholera is a severe diarrheal illness which affects millions of people annually. Those most affected reside in developing countries where outbreaks can cause a devastating healthcare crisis. Despite this, much is still unknown regarding the longevity of protective immune responses or how they are generated and maintained. This includes aspects of the mucosal response where immunity is induced, as well as features of the early immune response that could predict long-term immunity. To address these issues, we examined primary humoral immune responses following administration of a live attenuated cholera vaccine to 12 human participants. This study provides insight into the development of humoral immunity and information that may prove valuable for improving cholerae vaccines and treatments.
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DOI：
10.1084/jem.20080039
发表时间：
2008-10-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hammerschmidt SI;Ahrendt M;Bode U;Wahl B;Kremmer E;Förster R;Pabst O
通讯作者：
Pabst O
影响因子：
--
作者：
Aktar, Amena;Rahman, M. Arifur;Ryan, Edward T.
通讯作者：
Ryan, Edward T.
影响因子：
--
作者：
Haney, Douglas J.;Lock, Michael D.;Gurwith, Marc
通讯作者：
Gurwith, Marc
影响因子：
--
作者：
Johnson, Russell A.;Uddin, Taher;Ryan, Edward T.
通讯作者：
Ryan, Edward T.
毒素，毒素调节的菌毛和毒素调节剂对于人类的弧菌发病机理至关重要。
影响因子：
15.3
作者：
HERRINGTON, DA;HALL, RH;LOSONSKY, G;MEKALANOS, JJ;TAYLOR, RK;LEVINE, MM
通讯作者：
LEVINE, MM