Gut-Homing Conventional Plasmablasts and CD27(-) Plasmablasts Elicited after a Short Time of Exposure to an Oral Live-Attenuated Shigella Vaccine Candidate in Humans.
Gut-Homing Conventional Plasmablasts and CD27(-) Plasmablasts Elicited after a Short Time of Exposure to an Oral Live-Attenuated Shigella Vaccine Candidate in Humans.
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DOI：
10.3389/fimmu.2014.00374
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发表时间：
2014
影响因子：
7.3
通讯作者：
Sztein MB
中科院分区：
文献类型：
--
作者：
Toapanta FR;Simon JK;Barry EM;Pasetti MF;Levine MM;Kotloff KL;Sztein MB
目前，还没有获得许可的志贺氏菌疫苗，但出现了许多有希望的减毒活疫苗候选，包括CVD1208S(Δguaba，ΔSet，Δsen S.Flneri 2a)，它在一期临床试验中被证明是安全的和免疫原性的。在这里，我们报告了在门诊第二阶段临床试验中，受试者接种了CVD1208S疫苗后产生的免疫反应。CVD1208S口服免疫可产生较高的抗S抗体。免疫后7 天外周血中可见福氏2a内毒素和IPAB抗体反应及急性浆母细胞(PB)浸润。PB根据其归巢分子的表达进行分类，证实表达整合素α4β7的细胞或与CD62L联合表达的细胞负责抗体的产生(ELISpot测量)。免疫后第7天，用高色流式细胞仪观察常规外周血(CpB、CD19dim CD20CD27+高CD38+高CD3−)和不表达CD27的外周血(CD27−PB；前浆母细胞)的出现。归巢标志物(整合素α4、β7、CD62L、CXCR3和CXCR4)单独或同时表达的模式表明，CPB细胞优先归巢于炎症的肠粘膜。相反，~50%的CD27−PB细胞似乎是外周淋巴器官的归宿，或在整合素α4β7上调之前处于过渡状态。总之，这些观察表明，在短时间接触志贺氏菌口服疫苗后，可以激发强烈的免疫反应，包括可能归巢于肠道和其他次级淋巴器官的不同的PB亚群。
Currently, there is no licensed Shigella vaccine; however, various promising live-attenuated vaccine candidates have emerged, including CVD1208S (ΔguaBA, Δset, Δsen S. flexneri 2a), which was shown to be safe and immunogenic in Phase 1 clinical trials. Here, we report the immune responses elicited in an outpatient Phase 2 clinical trial in which subjects were vaccinated with CVD 1208S. Oral immunization with CVD 1208S elicited high anti-S. flexneri 2a LPS and IpaB antibody responses as well as an acute plasmablast (PB) infiltration in peripheral blood 7 days after immunization. PB sorted based on their expression of homing molecules confirmed that cells expressing integrin α4β7 alone or in combination with CD62L were responsible for antibody production (as measured by ELISpot). Furthermore, using high-color flow-cytometry, on day 7 after immunization, we observed the appearance of conventional PB (CPB, CD19dim CD20− CD27+high CD38+high CD3−), as well as a PB population that did not express CD27 (CD27− PB; pre-plasmablasts). The pattern of individual or simultaneous expression of homing markers (integrin α4β7, CD62L, CXCR3, and CXCR4) suggested that CPB cells homed preferentially to the inflamed gut mucosa. In contrast, ~50% CD27− PB cells appear to home to yet to be identified peripheral lymphoid organs or were in a transition state preceding integrin α4β7 upregulation. In sum, these observations demonstrate that strong immune responses, including distinct PB subsets with the potential to home to the gut and other secondary lymphoid organs, can be elicited after a short time of exposure to a shigella oral vaccine.
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影响因子：
7.3
作者：
Fink K
通讯作者：
Fink K
DOI：
10.1084/jem.20010670
发表时间：
2002-01-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bowman EP;Kuklin NA;Youngman KR;Lazarus NH;Kunkel EJ;Pan J;Greenberg HB;Butcher EC
通讯作者：
Butcher EC
影响因子：
4.9
作者：
Endt, Kathrin;Maier, Lisa;Hardt, Wolf-Dietrich
通讯作者：
Hardt, Wolf-Dietrich
影响因子：
3.1
作者：
BARZU, S;NATO, F;PHALIPON, A
通讯作者：
PHALIPON, A
影响因子：
5.5
作者：
Halliley, Jessica L.;Kyu, Shuya;Lee, F. Eun-Hyung
通讯作者：
Lee, F. Eun-Hyung