Evaluation of a Live Attenuated S. sonnei Vaccine Strain in the Human Enteroid Model.
Evaluation of a Live Attenuated S. sonnei Vaccine Strain in the Human Enteroid Model.
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DOI：
10.3390/pathogens10091079
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发表时间：
2021-08-25
期刊：
影响因子：
--
通讯作者：
Barry EM
中科院分区：
文献类型：
--
作者：
Pilla G;Wu T;Grassel C;Moon J;Foulke-Abel J;Tang CM;Barry EM
志贺氏菌是全球细菌性痢疾的主要病因，造成高死亡率，特别是中低收入国家五岁以下儿童的高死亡率。索尼氏志贺氏菌普遍存在于高收入国家，并在出现多重耐药菌株的工业化国家日益流行，成为一个重大的公共卫生问题。对抗索内氏沙门氏菌耐药性的一个策略是开发有效的疫苗。目前还没有获得许可的志贺氏菌疫苗，而且由于缺乏有效的小动物模型，这种疫苗的开发受到了阻碍。在这项工作中，我们首次使用人类肠道作为模型系统来评估质粒稳定的sonnei沙门氏菌减毒活疫苗菌株CVD 1233-SP和表达产肠毒素大肠杆菌抗原的多价衍生物CVD 1233-SP::CS2-CS3。这些菌株还在豚鼠模型中进行了免疫原性和保护能力测试，证明它们能够引起血清和粘膜抗体反应，并对野生型索内沙门氏菌的攻击具有保护作用。这些有希望的结果突出了肠样菌作为评估志贺氏菌候选疫苗的创新临床前模型的效用，构成了针对这一重要人类病原体制定预防策略的重大进展。
Shigella is a leading cause of bacillary dysentery worldwide, responsible for high death rates especially among children under five in low–middle income countries. Shigella sonnei prevails in high-income countries and is becoming prevalent in industrializing countries, where multi-drug resistant strains have emerged, as a significant public health concern. One strategy to combat drug resistance in S. sonnei is the development of effective vaccines. There is no licensed vaccine against Shigella, and development has been hindered by the lack of an effective small-animal model. In this work, we used human enteroids, for the first time, as a model system to evaluate a plasmid-stabilized S. sonnei live attenuated vaccine strain, CVD 1233-SP, and a multivalent derivative, CVD 1233-SP::CS2-CS3, which expresses antigens from enterotoxigenic Escherichia coli. The strains were also tested for immunogenicity and protective capacity in the guinea pig model, demonstrating their ability to elicit serum and mucosal antibody responses as well as protection against challenge with wild-type S. sonnei. These promising results highlight the utility of enteroids as an innovative preclinical model to evaluate Shigella vaccine candidates, constituting a significant advance for the development of preventative strategies against this important human pathogen.
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影响因子：
3.5
作者：
CHEREPANOV, PP;WACKERNAGEL, W
通讯作者：
WACKERNAGEL, W
影响因子：
4.2
作者：
Collins, Jennifer P.;Friedman, Cindy R.;Watkins, Louise Francois
通讯作者：
Watkins, Louise Francois
影响因子：
168.9
作者：
Kotloff, Karen L.;Nataro, James P.;Levine, Myron M.
通讯作者：
Levine, Myron M.
DOI：
10.1016/j.jcmgh.2015.10.001
发表时间：
2016-01-01
影响因子：
7.2
作者：
In J;Foulke-Abel J;Zachos NC;Hansen AM;Kaper JB;Bernstein HD;Halushka M;Blutt S;Estes MK;Donowitz M;Kovbasnjuk O
通讯作者：
Kovbasnjuk O
影响因子：
29.4
作者：
Foulke-Abel J;In J;Yin J;Zachos NC;Kovbasnjuk O;Estes MK;de Jonge H;Donowitz M
通讯作者：
Donowitz M