Characterization of ShigETEC, a Novel Live Attenuated Combined Vaccine against Shigellae and ETEC.
Characterization of ShigETEC, a Novel Live Attenuated Combined Vaccine against Shigellae and ETEC.
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新型志贺氏菌ETEC减毒活疫苗的特性研究。
DOI：
10.3390/vaccines8040689
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发表时间：
2020-11-16
期刊：
影响因子：
7.8
通讯作者：
Henics T
中科院分区：
文献类型：
--
作者：
Harutyunyan S;Neuhauser I;Mayer A;Aichinger M;Szijártó V;Nagy G;Nagy E;Girardi P;Malinoski FJ;Henics T
背景：志贺氏杆菌和产肠毒素大肠杆菌（ETEC）仍然是世界范围内引起腹泻疾病的两种主要细菌。开发针对志贺氏菌和ETEC的预防性疫苗的尝试尚未取得成功。广泛的志贺氏菌疫苗面临的主要挑战是血清型特异性免疫反应，否则具有保护作用的LPS o抗原。ETEC疫苗主要依靠热不稳定肠毒素（LT），而热稳定毒素（ST）也已被证明是一个重要的毒力因子。方法：我们构建了志贺氏菌和ETEC联合疫苗（ShigETEC），该疫苗基于志贺氏菌减毒活菌株，具有粗糙和非侵入性，异源表达两种ETEC抗原，LTB和STN12S脱毒版本。在相关动物模型上对该疫苗株进行了表征和免疫原性试验。结果：志贺氏菌tec免疫小鼠肺志贺氏菌病模型具有血清型不依赖的保护作用，可诱导抗细菌裂解物的高滴度IgG和IgA抗体，以及具有中和能力的抗志贺氏菌毒素抗体。结论：志贺氏菌ETEC是一种有前景的口服志贺氏菌和志贺氏菌ETEC感染候选疫苗，目前处于1期试验阶段。
Background: Shigella spp. and enterotoxigenic Escherichia coli (ETEC) remain the two leading bacterial causes of diarrheal diseases worldwide. Attempts to develop preventive vaccines against Shigella and ETEC have not yet been successful. The major challenge for a broad Shigella vaccine is the serotype-specific immune response to the otherwise protective LPS O-antigen. ETEC vaccines mainly rely on the heat-labile enterotoxin (LT), while heat-stable toxin (ST) has also been shown to be an important virulence factor. Methods: We constructed a combined Shigella and ETEC vaccine (ShigETEC) based on a live attenuated Shigella strain rendered rough and non-invasive with heterologous expression of two ETEC antigens, LTB and a detoxified version of ST (STN12S). This new vaccine strain was characterized and tested for immunogenicity in relevant animal models. Results: Immunization with ShigETEC resulted in serotype independent protection in the mouse lung shigellosis model and induced high titer IgG and IgA antibodies against bacterial lysates, and anti-ETEC toxin antibodies with neutralizing capacity. Conclusions: ShigETEC is a promising oral vaccine candidate against Shigella and ETEC infections and currently in Phase 1 testing.
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影响因子：
3.8
作者：
Liu CN;Lou ZZ;Li L;Yan HB;Blair D;Lei MT;Cai JZ;Fan YL;Li JQ;Fu BQ;Yang YR;McManus DP;Jia WZ
通讯作者：
Jia WZ
影响因子：
168.9
作者：
Kotloff, Karen L.;Nataro, James P.;Levine, Myron M.
通讯作者：
Levine, Myron M.
影响因子：
3.1
作者：
CLEMENTS, JD
通讯作者：
CLEMENTS, JD
影响因子：
5.5
作者：
Bourgeois, A. Louis;Wierzba, Thomas F.;Walker, Richard I.
通讯作者：
Walker, Richard I.
影响因子：
5.2
作者：
Rojas-Lopez M;Monterio R;Pizza M;Desvaux M;Rosini R
通讯作者：
Rosini R