Enhanced protective immunity against SARS-CoV-2 elicited by a VSV vector expressing a chimeric spike protein
Abstract 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-...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2021-11-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-021-00797-9 |
| _version_ | 1798033021838819328 |
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| author | Hongyue Li Yuhang Zhang Dong Li Yong-Qiang Deng Hongde Xu Chaoyue Zhao Jiandong Liu Dan Wen Jianguo Zhao Yongchun Li Yong Wu Shujun Liu Jiankai Liu Junfeng Hao Fei Yuan Shuguang Duo Cheng-Feng Qin Aihua Zheng |
| author_facet | Hongyue Li Yuhang Zhang Dong Li Yong-Qiang Deng Hongde Xu Chaoyue Zhao Jiandong Liu Dan Wen Jianguo Zhao Yongchun Li Yong Wu Shujun Liu Jiankai Liu Junfeng Hao Fei Yuan Shuguang Duo Cheng-Feng Qin Aihua Zheng |
| author_sort | Hongyue Li |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-11T20:22:30Z |
| format | Article |
| id | doaj.art-20ce20681e0349298e8a21ba9531574e |
| institution | Directory Open Access Journal |
| issn | 2059-3635 |
| language | English |
| last_indexed | 2024-04-11T20:22:30Z |
| publishDate | 2021-11-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj.art-20ce20681e0349298e8a21ba9531574e2022-12-22T04:04:46ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352021-11-016111210.1038/s41392-021-00797-9Enhanced protective immunity against SARS-CoV-2 elicited by a VSV vector expressing a chimeric spike proteinHongyue Li0Yuhang Zhang1Dong Li2Yong-Qiang Deng3Hongde Xu4Chaoyue Zhao5Jiandong Liu6Dan Wen7Jianguo Zhao8Yongchun Li9Yong Wu10Shujun Liu11Jiankai Liu12Junfeng Hao13Fei Yuan14Shuguang Duo15Cheng-Feng Qin16Aihua Zheng17State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of SciencesShenzhen Kangtai, Biotechnology Co., LtdState Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical SciencesSchool of Pharmaceutical Sciences, Zhengzhou UniversityState Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of SciencesShenzhen Kangtai, Biotechnology Co., LtdState Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Stem cell and Reproductive Biology, Institute of Zoology, Chinese Academy of SciencesSchool of Pharmaceutical Sciences, Zhengzhou UniversityDivision of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug ControlLaboratory Animal Center, Institute of Zoology, Chinese Academy of SciencesShenzhen Kangtai, Biotechnology Co., LtdCore Facility for Protein Research, Institute of Biophysics, Chinese Academy of SciencesState Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of SciencesLaboratory Animal Center, Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical SciencesState Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of SciencesAbstract 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.https://doi.org/10.1038/s41392-021-00797-9 |
| spellingShingle | Hongyue Li Yuhang Zhang Dong Li Yong-Qiang Deng Hongde Xu Chaoyue Zhao Jiandong Liu Dan Wen Jianguo Zhao Yongchun Li Yong Wu Shujun Liu Jiankai Liu Junfeng Hao Fei Yuan Shuguang Duo Cheng-Feng Qin Aihua Zheng Enhanced protective immunity against SARS-CoV-2 elicited by a VSV vector expressing a chimeric spike protein Signal Transduction and Targeted Therapy |
| title | Enhanced protective immunity against SARS-CoV-2 elicited by a VSV vector expressing a chimeric spike protein |
| title_full | Enhanced protective immunity against SARS-CoV-2 elicited by a VSV vector expressing a chimeric spike protein |
| title_fullStr | Enhanced protective immunity against SARS-CoV-2 elicited by a VSV vector expressing a chimeric spike protein |
| title_full_unstemmed | Enhanced protective immunity against SARS-CoV-2 elicited by a VSV vector expressing a chimeric spike protein |
| title_short | Enhanced protective immunity against SARS-CoV-2 elicited by a VSV vector expressing a chimeric spike protein |
| title_sort | enhanced protective immunity against sars cov 2 elicited by a vsv vector expressing a chimeric spike protein |
| url | https://doi.org/10.1038/s41392-021-00797-9 |
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