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-...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Medicine R Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/20ce20681e0349298e8a21ba9531574e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:20ce20681e0349298e8a21ba9531574e
record_format	dspace
spelling	oai:doaj.org-article:20ce20681e0349298e8a21ba9531574e2021-11-14T12:10:45ZEnhanced protective immunity against SARS-CoV-2 elicited by a VSV vector expressing a chimeric spike protein10.1038/s41392-021-00797-92059-3635https://doaj.org/article/20ce20681e0349298e8a21ba9531574e2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41392-021-00797-9https://doaj.org/toc/2059-3635Abstract 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.Hongyue LiYuhang ZhangDong LiYong-Qiang DengHongde XuChaoyue ZhaoJiandong LiuDan WenJianguo ZhaoYongchun LiYong WuShujun LiuJiankai LiuJunfeng HaoFei YuanShuguang DuoCheng-Feng QinAihua ZhengNature Publishing GrouparticleMedicineRBiology (General)QH301-705.5ENSignal Transduction and Targeted Therapy, Vol 6, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Biology (General) QH301-705.5
spellingShingle	Medicine R Biology (General) QH301-705.5 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
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.
format	article
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
title	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_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_sort	enhanced protective immunity against sars-cov-2 elicited by a vsv vector expressing a chimeric spike protein
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/20ce20681e0349298e8a21ba9531574e
work_keys_str_mv	AT hongyueli enhancedprotectiveimmunityagainstsarscov2elicitedbyavsvvectorexpressingachimericspikeprotein AT yuhangzhang enhancedprotectiveimmunityagainstsarscov2elicitedbyavsvvectorexpressingachimericspikeprotein AT dongli enhancedprotectiveimmunityagainstsarscov2elicitedbyavsvvectorexpressingachimericspikeprotein AT yongqiangdeng enhancedprotectiveimmunityagainstsarscov2elicitedbyavsvvectorexpressingachimericspikeprotein AT hongdexu enhancedprotectiveimmunityagainstsarscov2elicitedbyavsvvectorexpressingachimericspikeprotein AT chaoyuezhao enhancedprotectiveimmunityagainstsarscov2elicitedbyavsvvectorexpressingachimericspikeprotein AT jiandongliu enhancedprotectiveimmunityagainstsarscov2elicitedbyavsvvectorexpressingachimericspikeprotein AT danwen enhancedprotectiveimmunityagainstsarscov2elicitedbyavsvvectorexpressingachimericspikeprotein AT jianguozhao enhancedprotectiveimmunityagainstsarscov2elicitedbyavsvvectorexpressingachimericspikeprotein AT yongchunli enhancedprotectiveimmunityagainstsarscov2elicitedbyavsvvectorexpressingachimericspikeprotein AT yongwu enhancedprotectiveimmunityagainstsarscov2elicitedbyavsvvectorexpressingachimericspikeprotein AT shujunliu enhancedprotectiveimmunityagainstsarscov2elicitedbyavsvvectorexpressingachimericspikeprotein AT jiankailiu enhancedprotectiveimmunityagainstsarscov2elicitedbyavsvvectorexpressingachimericspikeprotein AT junfenghao enhancedprotectiveimmunityagainstsarscov2elicitedbyavsvvectorexpressingachimericspikeprotein AT feiyuan enhancedprotectiveimmunityagainstsarscov2elicitedbyavsvvectorexpressingachimericspikeprotein AT shuguangduo enhancedprotectiveimmunityagainstsarscov2elicitedbyavsvvectorexpressingachimericspikeprotein AT chengfengqin enhancedprotectiveimmunityagainstsarscov2elicitedbyavsvvectorexpressingachimericspikeprotein AT aihuazheng enhancedprotectiveimmunityagainstsarscov2elicitedbyavsvvectorexpressingachimericspikeprotein
_version_	1718429393334829056

Enhanced protective immunity against SARS-CoV-2 elicited by a VSV vector expressing a chimeric spike protein

Ejemplares similares