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新世界灵长类动物南迪熊猴致病性 CS17 和 CS19 肠毒素性大肠杆菌攻毒模型的建立和验证。

Establishment and Validation of Pathogenic CS17 and CS19 Enterotoxigenic Escherichia coli Challenge Models in the New World Primate Aotus nancymaae.

机构信息

Bacteriology Department, Naval Medical Research Unit No. 6, APO, Lima, Peru

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.

出版信息

Infect Immun. 2021 Feb 16;89(3). doi: 10.1128/IAI.00479-20.

Abstract

Enterotoxigenic (ETEC) is a common cause of diarrheal illness in the military, travelers, and children living in low- to middle-income countries. Increased antibiotic resistance, the absence of a licensed vaccine, and the lack of broadly practical therapeutics perpetuate the significant health and financial burden resulting from ETEC infection. A critical step in the evaluation of vaccines and therapeutics is preclinical screening in a relevant animal disease model that closely replicates human disease. We previously developed a diarrheal model of class 5a colonization factor (CF) CFA/I-expressing ETEC in the New World owl monkey species using ETEC strain H10407. In order to broaden the use of the model, we report here on the development of models of ETEC expressing the class 5b CFs CS17 and CS19 with strains LSN03-016011/A and WS0115A, respectively. For both models, we observed diarrheal attack rates of ≥80% after oral inoculation with 5 × 10 CFU of bacteria. These models will aid in assessing the efficacy of future ETEC vaccine candidates and therapeutics.

摘要

产肠毒素性(ETEC)是军队、旅行者和生活在中低收入国家的儿童腹泻病的常见病因。抗生素耐药性的增加、缺乏许可疫苗以及缺乏广泛实用的治疗方法,使 ETEC 感染造成的重大健康和财政负担持续存在。疫苗和疗法评估的关键步骤是在密切模拟人类疾病的相关动物疾病模型中进行临床前筛选。我们之前使用 ETEC 菌株 H10407 在新世界猫头鹰猴物种中开发了表达 5a 类定植因子(CF)CFA/I 的腹泻模型。为了扩大该模型的用途,我们在此报告了分别用菌株 LSN03-016011/A 和 WS0115A 表达 5b 类 CFs CS17 和 CS19 的 ETEC 模型的开发情况。对于这两种模型,我们观察到经口接种 5×10 CFU 细菌后,腹泻攻击率均≥80%。这些模型将有助于评估未来 ETEC 疫苗候选物和疗法的疗效。

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