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5 型腺病毒载体递送的尼帕病毒附着糖蛋白胞外域引发针对尼帕病毒和亨德拉病毒的广泛免疫应答。

Nipah virus attachment glycoprotein ectodomain delivered by type 5 adenovirus vector elicits broad immune response against NiV and HeV.

机构信息

Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, China.

College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.

出版信息

Front Cell Infect Microbiol. 2023 Jul 27;13:1180344. doi: 10.3389/fcimb.2023.1180344. eCollection 2023.

DOI:10.3389/fcimb.2023.1180344
PMID:37577376
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10413271/
Abstract

Nipah virus (NiV) and Hendra virus (HeV) are newly emerging dangerous zoonotic pathogens of the genus of the family. NiV and HeV (HNVs) which are transmitted by bats cause acute respiratory disease and fatal encephalitis in humans. To date, as there is a lack of antiviral drugs or effective antiviral therapies, the development of vaccines against those two viruses is of primary importance, and the immunogen design is crucial to the success of vaccines. In this study, the full-length protein (G), the ectodomain (Ge) and the head domain (Gs) of NiV attachment glycoprotein were delivered by the replication-defective type 5 adenovirus vector (Ad5) respectively, and the recombinant Ad5-NiV vaccine candidates (Ad5-NiVG, Ad5-NiVGe and Ad5-NiVGs) were constructed and their immunogenicity were evaluated in mice. The results showed that all the vaccine candidates stimulated specific humoral and cellular immune responses efficiently and rapidly against both NiV and HeV, and the Ad5-NiVGe elicited the strongest immune responses after a single-dose immunization. Furthermore, the potent conserved T-cell epitope DTLYFPAVGFL shared by NiV and HeV was identified in the study, which may provide valid information on the mechanism of HNVs-specific cellular immunity. In summary, this study demonstrates that the Ad5-NiVGe could be a potent vaccine candidate against HNVs by inducing robust humoral and cellular immune responses.

摘要

尼帕病毒(NiV)和亨德拉病毒(HeV)是新近出现的危险人畜共患病原体,属于副黏病毒科。通过蝙蝠传播的 NiV 和 HeV(HNVs)会导致人类急性呼吸道疾病和致命性脑炎。迄今为止,由于缺乏抗病毒药物或有效的抗病毒疗法,针对这两种病毒的疫苗开发至关重要,而免疫原设计是疫苗成功的关键。在这项研究中,我们分别使用复制缺陷型 5 型腺病毒载体(Ad5)传递了全长蛋白(G)、包膜区(Ge)和头部区(Gs),构建了重组 Ad5-NiV 疫苗候选物(Ad5-NiVG、Ad5-NiVGe 和 Ad5-NiVGs),并在小鼠中评估了它们的免疫原性。结果表明,所有疫苗候选物均能高效快速地诱导针对 NiV 和 HeV 的特异性体液和细胞免疫反应,单次免疫后 Ad5-NiVGe 引发的免疫反应最强。此外,研究还鉴定出 NiV 和 HeV 共有的保守 T 细胞表位 DTLYFPAVGFL,这可能为 HNVs 特异性细胞免疫的机制提供了有价值的信息。综上所述,本研究表明,Ad5-NiVGe 可通过诱导强烈的体液和细胞免疫反应成为一种有效的 HNVs 疫苗候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5136/10413271/0ee4e64e808c/fcimb-13-1180344-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5136/10413271/7f8010a45f35/fcimb-13-1180344-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5136/10413271/59ce9d6429dc/fcimb-13-1180344-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5136/10413271/85b583e9ca84/fcimb-13-1180344-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5136/10413271/29b8f8846a64/fcimb-13-1180344-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5136/10413271/22fd685d0b32/fcimb-13-1180344-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5136/10413271/0ee4e64e808c/fcimb-13-1180344-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5136/10413271/7f8010a45f35/fcimb-13-1180344-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5136/10413271/59ce9d6429dc/fcimb-13-1180344-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5136/10413271/85b583e9ca84/fcimb-13-1180344-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5136/10413271/29b8f8846a64/fcimb-13-1180344-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5136/10413271/22fd685d0b32/fcimb-13-1180344-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5136/10413271/0ee4e64e808c/fcimb-13-1180344-g006.jpg

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A potent Henipavirus cross-neutralizing antibody reveals a dynamic fusion-triggering pattern of the G-tetramer.一种有效的亨尼帕病毒交叉中和抗体揭示了 G-四聚体的动态融合触发模式。
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