Enteric Diseases Department, Naval Medical Research Center, Silver Spring, Maryland, USA.
Bacteriology Department, Naval Medical Research Unit No. 6, Lima, Peru.
Infect Immun. 2019 Jan 24;87(2). doi: 10.1128/IAI.00634-18. Print 2019 Feb.
The establishment of an animal model that closely approximates enterotoxigenic (ETEC) disease in humans is critical for the development and evaluation of vaccines against this enteropathogen. Here, we evaluated the susceptibility of , a New World monkey species, to ETEC infection. Animals were challenged orogastrically with 10 to 10 CFU of the human pathogenic CFA/I ETEC strain H10407 and examined for evidence of diarrhea and fecal shedding of bacteria. A clear dose-range effect was obtained, with diarrheal attack rates of 40% to 80%, validated in a follow-on study demonstrating an attack rate of 80% with 10 CFU of H10407 ETEC. To determine whether this model is an effective approach for assessing ETEC vaccine candidates, we used it to evaluate the ability of the donor strand-complemented CFA/I adhesin CfaE (dscCfaE) to protect against H10407 challenge. In a series of experiments, animals were intranasally vaccinated with dscCfaE alone, dscCfaE with either cholera toxin B-subunit (CTB) or heat-labile toxin (LTB), or phosphate-buffered saline (PBS) alone and then challenged with 10 CFU of H10407. Control animals vaccinated with PBS had attack rates of 70 to 90% on challenge. Vaccination with dscCfaE, or dscCfaE admixed with CTB or LTB, resulted in a reduction of attack rates, with vaccine efficacies of 66.7% ( = 0.02), 77.7% ( = 0.006), and 42.9% ( = 0.370) to 83.3% ( = 0.041), respectively. In conclusion, we have shown the H10407 ETEC challenge of to be an effective, reproducible model of ETEC disease, and importantly, we have demonstrated that in this model, vaccination with the prototype vaccine candidate dscCfaE is protective against CF-homologous disease.
建立一种与人肠毒素性（ETEC）疾病非常相似的动物模型对于开发和评估针对这种肠病原体的疫苗至关重要。在这里，我们评估了新世界猴种的易感性，以感染 ETEC。动物通过口腔挑战给予 10 到 10 CFU 的人致病 CFA/I ETEC 菌株 H10407，并检查腹泻和细菌粪便脱落的证据。在后续研究中，我们获得了一个清晰的剂量范围效应，用 10 CFU 的 H10407 ETEC 攻击时，腹泻攻击率为 40%至 80%，验证了攻击率为 80%。为了确定该模型是否是评估 ETEC 疫苗候选物的有效方法，我们使用它来评估供体链互补 CFA/I 粘附素 CfaE（dscCfaE）保护免受 H10407 攻击的能力。在一系列实验中，动物通过鼻腔接种 dscCfaE 单独，dscCfaE 与霍乱毒素 B 亚单位（CTB）或不耐热毒素（LTB），或磷酸盐缓冲盐水（PBS）单独接种，然后用 10 CFU 的 H10407 攻击。用 PBS 接种的对照动物在攻击时有 70%至 90%的攻击率。用 dscCfaE 或 dscCfaE 与 CTB 或 LTB 混合接种，可降低攻击率，疫苗效力分别为 66.7%（=0.02）、77.7%（=0.006）和 42.9%（=0.370）至 83.3%（=0.041）。总之，我们已经表明，用 H10407 ETEC 攻击 可以成为一种有效的、可重复的 ETEC 疾病模型，重要的是，我们已经证明，在这种模型中，用原型疫苗候选物 dscCfaE 接种是针对 CF 同源疾病的保护性的。
