Enhanced protective immunity against SARS-CoV-2 elicited by a VSV vector expressing a chimeric spike protein Article Swipe
Hongyue Li
,
Yuhang Zhang
,
Dong Li
,
Yong‐Qiang Deng
,
Hongde Xu
,
Chaoyue Zhao
,
Jiandong Liu
,
Dan Wen
,
Jianguo Zhao
,
Yongchun Li
,
Yong Wu
,
Shu‐Jun Liu
,
Jiankai Liu
,
Junfeng Hao
,
Fei Yuan
,
Shuguang Duo
,
Cheng‐Feng Qin
,
Aihua Zheng
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1038/s41392-021-00797-9
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1038/s41392-021-00797-9
SARS-CoV-2 and SARS-CoV are genetically related coronavirus and share the same cellular receptor ACE2. By replacing the VSV glycoprotein with the spikes (S) of SARS-CoV-2 and SARS-CoV, we generated two replication-competent recombinant viruses, rVSV-SARS-CoV-2 and rVSV-SARS-CoV. Using wild-type and human ACE2 (hACE2) knock-in mouse models, we found a single dose of rVSV-SARS-CoV could elicit strong humoral immune response via both intranasal (i.n.) and intramuscular (i.m.) routes. Despite the high genetic similarity between SARS-CoV-2 and SARS-CoV, no obvious cross-neutralizing activity was observed in the immunized mice sera. In macaques, neutralizing antibody (NAb) titers induced by one i.n. dose of rVSV-SARS-CoV-2 were eight-fold higher than those by a single i.m. dose. Thus, our data indicates that rVSV-SARS-CoV-2 might be suitable for i.n. administration instead of the traditional i.m. immunization in human. Because rVSV-SARS-CoV elicited significantly stronger NAb responses than rVSV-SARS-CoV-2 in a route-independent manner, we generated a chimeric antigen by replacing the receptor binding domain (RBD) of SARS-CoV S with that from the SARS-CoV-2. rVSV expressing the chimera (rVSV-SARS-CoV/2-RBD) induced significantly increased NAbs against SARS-CoV-2 in mice and macaques than rVSV-SARS-CoV-2, with a safe Th1-biased response. Serum immunized with rVSV-SARS-CoV/2-RBD showed no cross-reactivity with SARS-CoV. hACE2 mice receiving a single i.m. dose of either rVSV-SARS-CoV-2 or rVSV-SARS-CoV/2-RBD were fully protected against SARS-CoV-2 challenge without obvious lesions in the lungs. Our results suggest that transplantation of SARS-CoV-2 RBD into the S protein of SARS-CoV might be a promising antigen design for COVID-19 vaccines.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1038/s41392-021-00797-9
- https://www.nature.com/articles/s41392-021-00797-9.pdf
- OA Status
- gold
- Cited By
- 38
- References
- 52
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3214003990
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W3214003990Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1038/s41392-021-00797-9Digital Object Identifier
- Title
-
Enhanced protective immunity against SARS-CoV-2 elicited by a VSV vector expressing a chimeric spike proteinWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-11-10Full publication date if available
- Authors
-
Hongyue Li, Yuhang Zhang, Dong Li, Yong‐Qiang Deng, Hongde Xu, Chaoyue Zhao, Jiandong Liu, Dan Wen, Jianguo Zhao, Yongchun Li, Yong Wu, Shu‐Jun Liu, Jiankai Liu, Junfeng Hao, Fei Yuan, Shuguang Duo, Cheng‐Feng Qin, Aihua ZhengList of authors in order
- Landing page
-
https://doi.org/10.1038/s41392-021-00797-9Publisher landing page
- PDF URL
-
https://www.nature.com/articles/s41392-021-00797-9.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.nature.com/articles/s41392-021-00797-9.pdfDirect OA link when available
- Concepts
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Virology, Biology, Chimera (genetics), Vero cell, Antibody, Neutralization, Immune system, Recombinant DNA, Immunology, Virus, Genetics, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
38Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 8, 2024: 4, 2023: 8, 2022: 18Per-year citation counts (last 5 years)
- References (count)
-
52Number of works referenced by this work
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-
10Other works algorithmically related by OpenAlex
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