Single dose recombinant VSV based vaccine elicits robust and durable neutralizing antibody against Hantaan virus
Single dose recombinant VSV based vaccine elicits robust and durable neutralizing antibody against Hantaan virus
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DOI：
10.1038/s41541-024-00814-2
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发表时间：
2024-02-10
期刊：
影响因子：
9.2
通讯作者：
Zhang，Fanglin
中科院分区：
文献类型：
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作者：
Zhang，Hui;Liu，He;Zhang，Fanglin
汉坦病毒（HTNV）是一种在东亚流行的致病性正汉坦病毒，已知可引起严重肾综合征出血热（HFRS），致死率高。然而，目前还没有美国食品和药物管理局（FDA）批准的针对这种病毒的疫苗。虽然灭活疫苗已在流行地区获得认证并使用了数十年，但由灭活疫苗诱导的中和抗体（NAb）滴度较低，免疫计划复杂，至少需要三次注射，时间大约为6个月至1年。基于复制能力的水疱性口炎病毒（VSV）疫苗在单次注射后提供长时间的保护。在这项研究中，我们通过替换VSV- g开放阅读框，成功地在VSV基因组中设计了HTNV糖蛋白（GP）。得到的重组rVSV-HTNV-GP获救，其免疫原性与HTNV相似。用rVSV-HTNV-GP免疫的BALB/c小鼠单次注射后显示出高滴度的抗HTNV抗体。值得注意的是，rVSV-HTNV-GP对首尔病毒（一种正汉他病毒）诱导的交叉反应性NAb应答高于连续注射三次灭活疫苗诱导的应答。在HTNV攻击后，rvsv -HTNV- gp免疫小鼠在多个组织中的病毒负荷大大减少，肺和肝脏的炎症几乎检测不到。此外，单次注射rVSV-HTNV-GP建立了延长的免疫记忆状态，因为nab持续了1年以上，并提供了长期的HTNV感染保护。我们的研究结果可以为进一步开发基于rvsv -HTNV- gp的HTNV疫苗提供支持，该疫苗具有简化的免疫计划。
Hantaan virus (HTNV) is a pathogenic orthohantavirus prevalent in East Asia that is known to cause hemorrhagic fever with severe renal syndrome (HFRS), which has a high fatality rate. However, a Food and Drug Administration (FDA)-approved vaccine is not currently available against this virus. Although inactivated vaccines have been certified and used in endemic regions for decades, the neutralizing antibody (NAb) titer induced by inactivated vaccines is low and the immunization schedule is complicated, requiring at least three injections spanning approximately 6 months to 1 year. Replication-competent vesicular stomatitis virus (VSV)-based vaccines provide prolonged protection after a single injection. In this study, we successfully engineered the HTNV glycoprotein (GP) in the VSV genome by replacing the VSV-G open reading frame. The resulting recombinant (r) rVSV-HTNV-GP was rescued, and the immunogenicity of GP was similar to that of HTNV. BALB/c mice immunized with rVSV-HTNV-GP showed a high titer of NAb against HTNV after a single injection. Notably, the cross-reactive NAb response induced by rVSV-HTNV-GP against Seoul virus (an orthohantavirus) was higher than that induced by three sequential injections of inactivated vaccines. Upon challenge with HTNV, rVSV-HTNV-GP-immunized mice showed a profoundly reduced viral burden in multiple tissues, and inflammation in the lungs and liver was nearly undetectable. Moreover, a single injection of rVSV-HTNV-GP established a prolonged immunological memory status as the NAbs were sustained for over 1 year and provided long-term protection against HTNV infection. The findings of our study can support further development of an rVSV-HTNV-GP-based HTNV vaccine with a simplified immunization schedule.