Graduate Program in Molecular Microbiology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111, USA.
Vaccine. 2010 Nov 10;28(48):7683-9. doi: 10.1016/j.vaccine.2010.09.039. Epub 2010 Sep 25.
Yersinia pestis, the causative organism of plague, is a zoonotic organism with a worldwide distribution. Although the last plague epidemic occurred in early 1900s, human cases continue to occur due to contact with infected wild animals. In this study, we have developed a reservoir-targeted vaccine against Y. pestis, to interrupt transmission of disease in wild animals as a potential strategy for decreasing human disease. A vaccinia virus delivery system was used to express the F1 capsular protein and the LcrV type III secretion component of Y. pestis as a fusion protein. Here we show that a single dose of this vaccine administered orally, generates a dose-dependent antibody response in mice. Antibody titers peak by 3 weeks after administration and remain elevated for a minimum of 45 weeks. Vaccination provided up to 100% protection against challenge with Y. pestis administered by intranasal challenge at 10 times the lethal dose with protection lasting a minimum of 45 weeks. An orally available, vaccinia virus expressed vaccine against Y. pestis may be a suitable vaccine for a reservoir targeted strategy for the prevention of enzootic plague.
鼠疫耶尔森菌是引起鼠疫的病原体，是一种分布广泛的人畜共患病原体。尽管上一次鼠疫流行发生在 20 世纪初，但由于与受感染的野生动物接触，人类病例仍在继续发生。在这项研究中，我们开发了一种针对鼠疫耶尔森菌的储存库靶向疫苗，以阻断野生动物中的疾病传播，作为减少人类疾病的潜在策略。我们使用痘苗病毒传递系统来表达鼠疫耶尔森菌的 F1 荚膜蛋白和 LcrV 型 III 分泌成分作为融合蛋白。在这里，我们表明，口服给予一剂这种疫苗，可在小鼠中引起剂量依赖性的抗体反应。抗体滴度在给药后 3 周达到峰值，并至少持续 45 周升高。接种疫苗可提供 100%的保护，免受通过鼻内挑战给予的 10 倍致死剂量的鼠疫耶尔森菌的挑战，保护作用至少持续 45 周。一种口服可用的、由痘苗病毒表达的鼠疫耶尔森菌疫苗可能是针对储存库的、用于预防地方性鼠疫的一种合适疫苗。
