Human endogenous retrovirus-enveloped baculoviral DNA vaccines against MERS-CoV and SARS-CoV2.

Human endogenous retrovirus-enveloped baculoviral DNA vaccines against MERS-CoV and SARS-CoV2.
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DOI:
10.1038/s41541-021-00303-w
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发表时间:
2021-03-19
期刊:
影响因子:
9.2
通讯作者:
Kim YB
Kim YB
中科院分区:
医学1区
文献类型:
--
作者:
Cho H;Jang Y;Park KH;Choi H;Nowakowska A;Lee HJ;Kim M;Kang MH;Kim JH;Shin HY;Oh YK;Kim YB

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本文报道了一种基于重组杆状病毒载体的中东呼吸综合征冠状病毒(MERS-CoV)和严重急性呼吸综合征冠状病毒-2 (SARS-CoV2) DNA疫苗体系。构建了一种表达人内源性逆转录病毒包膜基因(AcHERV)的非复制型重组杆状病毒,并将其作为DNA疫苗载体转染人细胞。为了构建MERS-CoV疫苗,将编码MERS-CoV S-full、S1亚基或受体结合域(RBD)的DNA插入到AcHERV基因组中。在构建新冠病毒疫苗时,将编码SARS-CoV2 S-full或S1或融合MERS-CoV NTD结构域的SARS-CoV2 RBD的DNA插入到AcHERV基因组中。在动物模型中,AcHERV-DNA疫苗可诱导高体液和细胞介导免疫。在攻毒试验中,两次免疫的AcHERV-MERS-S1和acherv - covid - 19- s分别对MERS-CoV和SARS-CoV2表现出完全的保护作用。与AcHERV-MERS疫苗不同,acherv - covid - 19- s对SARS-CoV2的挑战提供了最大的保护。这些结果支持了AcHERV-MERS或acherv - covid - 19疫苗在预防病毒感染大流行传播方面的可行性。
Here we report a recombinant baculoviral vector-based DNA vaccine system against Middle East respiratory syndrome coronavirus (MERS-CoV) and the severe acute respiratory syndrome coronavirus-2 (SARS-CoV2). A non-replicating recombinant baculovirus expressing the human endogenous retrovirus envelope gene (AcHERV) was constructed as a DNA vaccine vector for gene delivery into human cells. For MERS-CoV vaccine construction, DNA encoding MERS-CoV S-full, S1 subunit, or receptor-binding domain (RBD) was inserted into the genome of AcHERV. For COVID19 vaccine construction, DNA encoding SARS-CoV2 S-full or S1 or a MERS-CoV NTD domain-fused SARS-CoV2 RBD was inserted into the genome of AcHERV. AcHERV-DNA vaccines induce high humoral and cell-mediated immunity in animal models. In challenge tests, twice immunized AcHERV-MERS-S1 and AcHERV-COVID19-S showed complete protection against MERS-CoV and SARS-CoV2, respectively. Unlike AcHERV-MERS vaccines, AcHERV-COVID19-S provided the greatest protection against SARS-CoV2 challenge. These results support the feasibility of AcHERV-MERS or AcHERV-COVID19 vaccines in preventing pandemic spreads of viral infections.
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