Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs.

Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs.
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表达拉沙病毒 GP1 和 GP2 糖蛋白的黄热病 17D 载体疫苗可为豚鼠提供针对致命疾病的保护。

DOI:
10.1016/j.vaccine.2010.11.079
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发表时间:
2011-02-01
期刊:
影响因子:
5.5
通讯作者:
Lukashevich, Igor S.
Lukashevich, Igor S.
中科院分区:
医学3区
文献类型:
--
作者:
Jiang, Xiaohong;Dalebout, Tim J.;Bredenbeek, Peter J.;Carrion, Ricardo, Jr.;Brasky, Kathleen;Patterson, Jean;Goicochea, Marco;Bryant, Joseph;Salvato, Maria S.;Lukashevich, Igor S.

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黄热病(YF)和拉沙热(LF)是西非共同流行的两种流行出血热,每年造成数千人死亡。YF疫苗17 D已被用作拉沙病毒糖蛋白前体(LASV-GPC)或其亚基GP 1(附着糖蛋白)和GP 2(融合糖蛋白)的载体。在YF 17 D E和NS 1基因之间克隆较短的插入片段LASV GP 1和GP 2,与YF 17 D/LASV GPC重组体相比,提高了重组病毒YF 17 D/LASV GP 1和-GP 2的遗传稳定性。重组病毒具有复制能力,并在感染细胞中正确加工YF和LASV GP蛋白。YF 17 D/LASV-GP 1和GP 2在小鼠中诱导特异性CD 8 + T细胞应答并保护13株豚鼠对抗致死性LF。与用减毒活疫苗ML 29免疫不同,用YF 17 D/LASV-GP 1和GP 2免疫不提供杀菌免疫。本研究证明了基于YF 17 D的疫苗在西非控制LF的可行性。
Yellow Fever (YF) and Lassa Fever (LF) are two prevalent hemorrhagic fevers co-circulating in West Africa and responsible for thousands of deaths annually. The YF vaccine 17D has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) or their subunits, GP1 (attachment glycoprotein) and GP2 (fusion glycoprotein). Cloning shorter inserts, LASV GP1 and GP2, between YF17D E and NS1 genes enhanced genetic stability of recombinant viruses, YF17D/LASV-GP1 and –GP2, in comparison with YF17D/LASV-GPC recombinant. The recombinant viruses were replication competent and properly processed YF and LASV GP proteins in infected cells. YF17D/LASV-GP1&GP2 induced specific CD8+ T cell responses in mice and protected strain 13 guinea pigs against fatal LF. Unlike immunization with live attenuated reassortant vaccine ML29, immunization with YF17D/LASV-GP1&GP2 did not provide sterilizing immunity. This study demonstrates the feasibility of YF17D-based vaccine to control LF in West Africa.
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