A novel Sin Nombre virus DNA vaccine and its inclusion in a candidate pan-hantavirus vaccine against hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS).
A novel Sin Nombre virus DNA vaccine and its inclusion in a candidate pan-hantavirus vaccine against hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS).
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DOI：
10.1016/j.vaccine.2013.07.025
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发表时间：
2013-09-13
期刊：
影响因子：
5.5
通讯作者：
Brocato, Rebecca
中科院分区：
文献类型：
--
作者：
Hooper, Jay W.;Josleyn, Matthew;Ballantyne, John;Brocato, Rebecca
Sin Nombre病毒（SNV;布尼亚病毒科，汉坦病毒属）在北美引起称为汉坦病毒肺综合征（HPS）的出血热。自1993年以来，美国约有200例HPS致死病例，主要发生在健康的工作年龄男性中（病死率为35%）。没有FDA批准的疫苗或药物来预防或治疗HPS。在此之前，我们报道了基于安第斯山脉病毒（ANDV）全长M基因片段的汉坦病毒疫苗在南美洲用于HPS，以及汉坦病毒（HTNV）和普马拉病毒（PUUV）在欧亚大陆用于肾综合征出血热（HFRS），都在动物模型中引发了高滴度的中和抗体。HFRS比HPS更流行（每年> 20，000例），但致病性较低（病死率1-15%）。在这里，我们报告的建设和测试的SNV全长M基因为基础的DNA疫苗，以防止HPS。通过肌肉电穿孔（mEP）接种SNV DNA疫苗的兔产生高滴度的中和抗体。此外，使用基因枪用SNV DNA疫苗接种三次的仓鼠完全免受SNV感染。这是第一种能特异性激发抗SNV高效价中和抗体的疫苗。为了测试产生泛汉坦病毒疫苗的可能性，通过mEP用HPS混合物（ANDV和SNV质粒）或HFRS混合物（HTNV和PUUV质粒）或HPS/HFRS混合物（所有四种质粒）接种兔。HPS混合物和HFRS混合物分别引起主要针对ANDV/SNV和HTNV/PUUV的中和抗体。此外，HPS/HFRS混合物引发了针对所有四种病毒的中和抗体。这些发现表明，使用混合质粒DNA疫苗方法的泛汉坦病毒疫苗是可行的，值得进一步开发。
Sin Nombre virus (SNV; family Bunyaviridae, genus Hantavirus) causes a hemorrhagic fever known as hantavirus pulmonary syndrome (HPS) in North America. There have been approximately 200 fatal cases of HPS in the United States since 1993, predominantly in healthy working-age males (case fatality rate 35%). There are no FDA-approved vaccines or drugs to prevent or treat HPS. Previously, we reported that hantavirus vaccines based on the full-length M gene segment of Andes virus (ANDV) for HPS in South America, and Hantaan virus (HTNV) and Puumala virus (PUUV) for hemorrhagic fever with renal syndrome (HFRS) in Eurasia, all elicited high-titer neutralizing antibodies in animal models. HFRS is more prevalent than HPS (>20,000 cases per year) but less pathogenic (case fatality rate 1–15%). Here, we report the construction and testing of a SNV full-length M gene-based DNA vaccine to prevent HPS. Rabbits vaccinated with the SNV DNA vaccine by muscle electroporation (mEP) developed high titers of neutralizing antibodies. Furthermore, hamsters vaccinated three times with the SNV DNA vaccine using a gene gun were completely protected against SNV infection. This is the first vaccine of any kind that specifically elicits high-titer neutralizing antibodies against SNV. To test the possibility of producing a pan-hantavirus vaccine, rabbits were vaccinated by mEP with an HPS mix (ANDV and SNV plasmids), or HFRS mix (HTNV and PUUV plasmids), or HPS/HFRS mix (all four plasmids). The HPS mix and HFRS mix elicited neutralizing antibodies predominantly against ANDV/SNV and HTNV/PUUV, respectively. Furthermore, the HPS/HFRS mix elicited neutralizing antibodies against all four viruses. These findings demonstrate a pan-hantavirus vaccine using a mixed-plasmid DNA vaccine approach is feasible and warrants further development.
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影响因子：
3.7
作者：
Fath S;Bauer AP;Liss M;Spriestersbach A;Maertens B;Hahn P;Ludwig C;Schäfer F;Graf M;Wagner R
通讯作者：
Wagner R
影响因子：
9.4
作者：
Elgh, F;Lundkvist, A;Juto, P
通讯作者：
Juto, P
影响因子：
5.5
作者：
Bharadwaj, M;Lyons, CR;Hjelle, B
通讯作者：
Hjelle, B
影响因子：
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作者：
Dupuy, Lesley C.;Richards, Michelle J.;Schmaljohn, Connie S.
通讯作者：
Schmaljohn, Connie S.
DOI：
10.4269/ajtmh.1994.51.102
发表时间：
1994-07-01
影响因子：
3.3
作者：
ELLIOTT, LH;KSIAZEK, TG;PETERS, CJ
通讯作者：
PETERS, CJ