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一种重组裂谷热病毒糖蛋白亚单位疫苗对牛异源强毒攻击提供完全保护的初步评估

Preliminary Evaluation of a Recombinant Rift Valley Fever Virus Glycoprotein Subunit Vaccine Providing Full Protection against Heterologous Virulent Challenge in Cattle.

作者信息

Wilson William C, Faburay Bonto, Trujillo Jessie D, Ragan Izabela, Sunwoo Sun-Young, Morozov Igor, Shivanna Vinay, Balogh Aaron, Urbaniak Kinga, McVey D Scott, Bold Dashzeveg, Gaudreault Natasha N, Schirtzinger Erin E, Ma Wenjun, Richt Juergen A

机构信息

United States Department of Agriculture, Agricultural Research Service, Arthropod Borne Animal Disease Research Unit, Manhattan, KS 66502, USA.

Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.

出版信息

Vaccines (Basel). 2021 Jul 6;9(7):748. doi: 10.3390/vaccines9070748.

Abstract

Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen that causes periodic outbreaks of abortion in ruminant species and hemorrhagic disease in humans in sub-Saharan Africa. These outbreaks have a significant impact on veterinary and public health. Its introduction to the Arabian Peninsula in 2003 raised concerns of further spread of this transboundary pathogen to non-endemic areas. These concerns are supported by the presence of competent vectors in many non-endemic countries. There is no licensed RVF vaccine available for humans and only a conditionally licensed veterinary vaccine available in the United States. Currently employed modified live attenuated virus vaccines in endemic countries lack the ability for differentiating infected from vaccinated animals (DIVA). Previously, the efficacy of a recombinant subunit vaccine based on the RVFV Gn and Gc glycoproteins, derived from the 1977 human RVFV isolate ZH548, was demonstrated in sheep. In the current study, cattle were vaccinated subcutaneously with the Gn only, or Gn and Gc combined, with either one or two doses of the vaccine and then subjected to heterologous virus challenge with the virulent Kenya-128B-15 RVFV strain, isolated from mosquitoes in 2006. The elicited immune responses by some vaccine formulations (one or two vaccinations) conferred complete protection from RVF within 35 days after the first vaccination. Vaccines given 35 days prior to RVFV challenge prevented viremia, fever and RVFV-associated histopathological lesions. This study indicates that a recombinant RVFV glycoprotein-based subunit vaccine platform is able to prevent and control RVFV infections in target animals.

摘要

裂谷热病毒(RVFV)是一种由蚊子传播的人畜共患病原体,在撒哈拉以南非洲地区可导致反刍动物周期性流产以及人类出血性疾病。这些疫情对兽医和公共卫生产生重大影响。2003年该病毒传入阿拉伯半岛,引发了对这种跨界病原体进一步传播至非流行地区的担忧。许多非流行国家存在适宜的传播媒介,这支持了上述担忧。目前尚无获许可的人用裂谷热疫苗,在美国仅有一种有条件许可的兽用疫苗。流行国家目前使用的减毒活疫苗缺乏区分感染动物和接种动物的能力(DIVA)。此前,基于1977年人裂谷热病毒分离株ZH548的Gn和Gc糖蛋白的重组亚单位疫苗在绵羊身上显示出了疗效。在本研究中,给牛皮下接种仅含Gn或Gn与Gc组合的疫苗,接种一剂或两剂,然后用2006年从蚊子中分离出的强毒株肯尼亚-128B-15裂谷热病毒进行异源病毒攻击。一些疫苗配方(接种一剂或两剂)引发的免疫反应在首次接种后35天内提供了对裂谷热的完全保护。在裂谷热病毒攻击前35天接种疫苗可预防病毒血症、发热以及与裂谷热病毒相关的组织病理学损伤。本研究表明,基于裂谷热病毒糖蛋白的重组亚单位疫苗平台能够预防和控制目标动物的裂谷热病毒感染。

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