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羊驼接种裂谷热病毒疫苗:MP - 12疫苗的安全性、免疫原性和致病性

Vaccination of alpacas against Rift Valley fever virus: Safety, immunogenicity and pathogenicity of MP-12 vaccine.

作者信息

Rissmann M, Ulrich R, Schröder C, Hammerschmidt B, Hanke D, Mroz C, Groschup M H, Eiden M

机构信息

Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.

Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.

出版信息

Vaccine. 2017 Jan 23;35(4):655-662. doi: 10.1016/j.vaccine.2016.12.003. Epub 2016 Dec 21.

DOI:10.1016/j.vaccine.2016.12.003
PMID:28012779
Abstract

Rift Valley fever (RVF) is an emerging zoonosis of major public health concern in Africa and Arabia. Previous outbreaks attributed camelids a significant role in the epidemiology of Rift Valley fever virus (RVFV), making them an important target species for vaccination. Using three alpacas as model-organisms for dromedary camels, the safety, immunogenicity and pathogenicity of the MP-12 vaccine were evaluated in this study. To compare both acute and subacute effects, animals were euthanized at 3 and 31days post infection (dpi). Clinical monitoring, analysis of liver enzymes and hematological parameters demonstrated the tolerability of the vaccine, as no significant adverse effects were observed. Comprehensive analysis of serological parameters illustrated the immunogenicity of the vaccine, eliciting high neutralizing antibody titers and antibodies targeting different viral antigens. RVFV was detected in serum and liver of the alpaca euthanized 3dpi, whereas no virus was detectable at 31dpi. Viral replication was confirmed by detection of various RVFV-antigens in hepatocytes by immunohistochemistry and the presence of mild multifocal necrotizing hepatitis. In conclusion, results indicate that MP-12 is a promising vaccine candidate but still has a residual pathogenicity, which requires further investigation.

摘要

裂谷热(RVF)是非洲和阿拉伯地区一种引起重大公共卫生关注的新发人畜共患病。以往的疫情表明骆驼科动物在裂谷热病毒(RVFV)的流行病学中起着重要作用,使其成为疫苗接种的重要目标物种。本研究以三只羊驼作为单峰骆驼的模型生物,评估了MP - 12疫苗的安全性、免疫原性和致病性。为了比较急性和亚急性效应,在感染后3天和31天对动物实施安乐死。临床监测、肝酶分析和血液学参数表明该疫苗具有耐受性,未观察到明显的不良反应。血清学参数的综合分析表明该疫苗具有免疫原性,可诱导产生高中和抗体滴度以及针对不同病毒抗原的抗体。在感染后3天实施安乐死的羊驼血清和肝脏中检测到RVFV,而在感染后31天未检测到病毒。通过免疫组织化学检测肝细胞中各种RVFV抗原以及存在轻度多灶性坏死性肝炎证实了病毒复制。总之,结果表明MP - 12是一种有前景的候选疫苗,但仍具有残余致病性,需要进一步研究。

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