Plasma and Mucosal Immunoglobulin M, Immunoglobulin A, and Immunoglobulin G Responses to the Vibrio cholerae O1 Protein Immunome in Adults With Cholera in Bangladesh

Plasma and Mucosal Immunoglobulin M, Immunoglobulin A, and Immunoglobulin G Responses to the Vibrio cholerae O1 Protein Immunome in Adults With Cholera in Bangladesh
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DOI:
10.1093/infdis/jix253
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发表时间:
2017-07-01
影响因子:
6.4
通讯作者:
Ryan, Edward T.
Ryan, Edward T.
中科院分区:
医学2区
文献类型:
--
作者:
Charles, Richelle C.;Nakajima, Rie;Ryan, Edward T.

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霍乱是由霍乱弧菌O 1或O 139引起的人类严重脱水性疾病。免疫原性霍乱弧菌抗原的鉴定可能会导致更好地了解人类cholera.We探测微阵列含有3652霍乱弧菌抗原与血浆和抗体在淋巴细胞上清液(ALS,粘膜免疫反应的替代标记物)从孟加拉国和年龄,性别和ABO相匹配的孟加拉国对照组的霍乱弧菌O 1引起的严重霍乱患者。我们使用酶联免疫吸附试验验证了一个已鉴定抗原的子集。总的来说,我们在筛选中鉴定了608种免疫反应性霍乱弧菌抗原,其中59种在恢复期与急性期或健康对照样品相比具有更高的免疫反应性(血浆中34种,粘膜ALS中39种;两种样品组均为13种)。所鉴定的抗原包括霍乱毒素B和A亚单位、霍乱弧菌特异性多糖和脂多糖、毒素共调节菌毛A、唾液酸酶、溶血素A、鞭毛蛋白(FlaB、FlaC和FlaD)、磷酸烯醇化酶-蛋白磷酸转移酶和二氨基丁酸-2-酮戊二酸氨基转移酶。它已经确定了可能有助于开发改进的霍乱疫苗的抗原。
Cholera is a severe dehydrating illness of humans caused by toxigenic strains of Vibrio cholerae O1 or O139. Identification of immunogenic V. cholerae antigens could lead to a better understanding of protective immunity in human cholera.We probed microarrays containing 3652 V. cholerae antigens with plasma and antibody-in-lymphocyte supernatant (ALS, a surrogate marker of mucosal immune responses) from patients with severe cholera caused by V. cholerae O1 in Bangladesh and age-, sex-, and ABO-matched Bangladeshi controls. We validated a subset of identified antigens using enzyme-linked immunosorbent assay.Overall, we identified 608 immunoreactive V. cholerae antigens in our screening, 59 of which had higher immunoreactivity in convalescent compared with acute-stage or healthy control samples (34 in plasma, 39 in mucosal ALS; 13 in both sample sets). Identified antigens included cholera toxin B and A subunits, V. cholerae O-specific polysaccharide and lipopolysaccharide, toxin coregulated pilus A, sialidase, hemolysin A, flagellins (FlaB, FlaC, and FlaD), phosphoenolpyruvate-protein phosphotransferase, and diaminobutyrate-2-oxoglutarate aminotransferase.This study is the first antibody profiling of the mucosal and systemic antibody responses to the nearly complete V. cholerae O1 protein immunome; it has identified antigens that may aid in the development of an improved cholera vaccine.