Development of a live attenuated antigenic marker classical swine fever vaccine
Development of a live attenuated antigenic marker classical swine fever vaccine
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DOI：
10.1016/j.virol.2008.10.039
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发表时间：
2009-02-05
期刊：
影响因子：
3.7
通讯作者：
Borca, M. V.
中科院分区：
文献类型：
--
作者：
Holinka, L. G.;Fernandez-Sainz, I.;Borca, M. V.
直到最近，控制经典猪瘟病毒（CSFV）的战略包括预防性接种疫苗或不接种疫苗，并根据受影响地理区域的流行病学情况消灭受感染的猪群。标记疫苗可以区分自然感染的猪和接种过疫苗的猪，可以补充“消灭”措施。本研究开发了一种双重抗原标记的猪瘟活减毒菌株FIagT4v，该菌株是由两个减毒基因决定因素结合而成。FIagT4v含有一个阳性抗原标记，合成Flag (R)表位，通过在E1糖蛋白中插入19mer引入；以及E2糖蛋白中单克隆抗体WH303 （mAbWH303）表位结合位点突变产生的阴性标记。经鼻或肌肉注射FIagT4v可在接种后早期（2或3天）和后期（28天）保护猪免受CSFV布雷西亚毒株的毒力。FIagT4v诱导的猪抗体反应对Flag表位反应强烈，但未能抑制mAbWH303与代表WH303表位的合成肽的结合。这些结果为合理设计猪瘟抗原标记减毒活病毒提供了概念证明。Elsevier Inc.出版。
Until recently strategies for controlling Classical Swine Fever Virus (CSFV) involve either prophylactic vaccination or non-vaccination with elimination of infected herds depending on the epidemiological situation of the affected geographical area. Marker vaccines allowing distinction between naturally infected from vaccinated swine could complement "stamping out" measures. Here we developed a double antigenic marker live attenuated CSFV strain FIagT4v obtained by combining two genetic determinants of attenuation. FIagT4v harbors a positive antigenic marker, synthetic Flag (R) epitope, introduced via a 19mer insertion in E1 glycoprotein; and a negative marker resulting from mutations of the binding site of monoclonal antibody WH303 (mAbWH303) epitope in E2 glycoprotein. Intranasal or intramuscular administration of FIagT4v protected swine against virulent CSFV Brescia strain at early (2 or 3 days), and late (28 days) time post-inoculation. FIagT4v induced antibody response in pigs reacted strongly against the Flag epitope but failed to inhibit binding of mAbWH303 to a synthetic peptide representing the WH303 epitope. These results constitute a proof-of-concept for rationally designing a CSFV antigenically marked live attenuated virus. Published by Elsevier Inc.