A live attenuated vaccine for Lassa fever made by reassortment of Lassa and Mopeia viruses
A live attenuated vaccine for Lassa fever made by reassortment of Lassa and Mopeia viruses
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DOI：
10.1128/jvi.79.22.13934-13942.2005
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发表时间：
2005-11-01
影响因子：
5.4
通讯作者：
Salvato, MS
中科院分区：
文献类型：
--
作者：
Lukashevich, IS;Patterson, J;Salvato, MS
拉沙病毒 (LASV) 和莫佩亚病毒 (MOPV) 是密切相关的旧世界沙粒病毒，它们可以在共感染期间交换基因组片段（重配）。克隆 ML29 选自 MOPV/LASV (MOP/LAS) 重配体文库，编码 LASV 的主要抗原（核衣壳和糖蛋白）以及 MOPV 的 RNA 聚合酶和锌结合蛋白。 ML29 的复制在豚鼠和非人灵长类动物中减弱。在小鼠过继转移实验中，低至 150 PFU 的 ML29 即可诱导保护性细胞介导的免疫。所有接种克隆 ML29 的 13 品系豚鼠在 IASV 攻击后至少存活 70 天，没有任何疾病体征或组织学损伤。接种克隆ML29的恒河猴发育出原代病毒特异性T细胞，能够分泌γ干扰素以响应同源MOP/LAS和异源MOPV以及淋巴细胞性脉络膜脑膜炎病毒。对感染这种 MOPV/LAS 重组病毒的两只恒河猴的详细检查显示没有组织学病变或疾病体征。因此，ML29 是一种有前途的拉沙热减毒疫苗候选物。
Lassa virus (LASV) and Mopeia virus (MOPV) are closely related Old World arenaviruses that can exchange genomic segments (reassort) during coinfection. Clone ML29, selected from a library of MOPV/LASV (MOP/LAS) reassortants, encodes the major antigens (nucleocapsid and glycoprotein) of LASV and the RNA polymerase and zinc-binding protein of MOPV. Replication of ML29 was attenuated in guinea pigs and nonhuman primates. In murine adoptive-transfer experiments, as little as 150 PFU of ML29 induced protective cell-mediated immunity. All strain 13 guinea pigs vaccinated with clone ML29 survived at least 70 days after IASV challenge without either disease signs or histological lesions. Rhesus macaques inoculated with clone ML29 developed primary virus-specific T cells capable of secreting gamma interferon in response to homologous MOP/LAS and heterologous MOPV and lymphocytic choriomeningitis virus. Detailed examination of two rhesus macaques infected with this MOPV/LAS reassortant revealed no histological lesions or disease signs. Thus, ML29 is a promising attenuated vaccine candidate for Lassa fever.