DNA vaccination with the Hantaan virus M gene protects hamsters against three of four HFRS hantaviruses and elicits a high-titer neutralizing antibody response in rhesus monkeys
DNA vaccination with the Hantaan virus M gene protects hamsters against three of four HFRS hantaviruses and elicits a high-titer neutralizing antibody response in rhesus monkeys
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DOI：
10.1128/jvi.75.18.8469-8477.2001
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发表时间：
2001-09-01
影响因子：
5.4
通讯作者：
Schmaljohn, CS
中科院分区：
文献类型：
--
作者：
Hooper, JW;Custer, DM;Schmaljohn, CS
已知四种汉坦病毒-汉坦病毒（HTNV）、首尔病毒（SEOV）、多布拉瓦病毒（DOBV）和普马拉病毒-在欧洲和亚洲引起肾综合征出血热（HFRS）。HTN-V导致最严重的HFRS形式（5至15%的病死率），每年折磨数万人。以前，我们证明了用表达SEOV M基因的质粒进行DNA疫苗接种可引起中和抗体，并保护仓鼠免受SEOV和HTNV感染。在这里，我们报告的建设和评价的DNA疫苗，表达HTNV M基因产物，G1和G2。用HTNV M基因对仓鼠进行DNA疫苗接种赋予针对HTNV、SEOV和DOBV感染的无菌保护。用SEOV或HTNV M基因对恒河猴进行DNA疫苗接种引起高水平的中和抗体。这是汉坦病毒DNA疫苗在非人灵长类动物中的第一个免疫原性数据。由于中和抗体反应被认为是人类保护性免疫的替代标志物，我们在仓鼠中的保护数据结合在猴子中的免疫原性数据表明，基于汉坦病毒M基因的DNA疫苗可以保护人类免受最严重形式的HFRS。
Four hantaviruses-Hantaan virus (HTNV), Seoul virus (SEOV), Dobrava virus (DOBV) and Puumala virus-are known to cause hemorrhagic fever with renal syndrome (HFRS) in Europe and Asia. HTN-V causes the most severe form of HFRS (5 to 15% case-fatality rate) and afflicts tens of thousands of people annually. Previously, we demonstrated that DNA vaccination with a plasmid expressing the SEOV M gene elicited neutralizing antibodies and protected hamsters against infection with SEOV and HTNV. Here, we report the construction and evaluation of a DNA vaccine that expresses the HTNV M gene products, G1 and G2. DNA vaccination of hamsters with the HTNV M gene conferred sterile protection against infection with HTNV, SEOV, and DOBV. DNA vaccination of rhesus monkeys with either the SEOV or HTNV M gene elicited high levels of neutralizing antibodies. These are the first immunogenicity data for hantavirus DNA vaccines in nonhuman primates. Because a neutralizing antibody response is considered a surrogate marker for protective immunity in humans, our protection data in hamsters combined with the immunogenicity data in monkeys suggest that hantavirus M gene-based DNA vaccines could protect humans against the most severe forms of HFRS.