RBD-Fc-based COVID-19 vaccine candidate induces highly potent SARS-CoV-2 neutralizing antibody response
The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed serious threats to global health and economy, thus calling for the development of safe and effective vaccines. The receptor-binding domain (RBD) in the spike protein o...
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Veröffentlicht in: | Signal transduction and targeted therapy 2020-11, Vol.5 (1), p.282-282, Article 282 |
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creator | Liu, Zezhong Xu, Wei Xia, Shuai Gu, Chenjian Wang, Xinling Wang, Qian Zhou, Jie Wu, Yanling Cai, Xia Qu, Di Ying, Tianlei Xie, Youhua Lu, Lu Yuan, Zhenghong Jiang, Shibo |
description | The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed serious threats to global health and economy, thus calling for the development of safe and effective vaccines. The receptor-binding domain (RBD) in the spike protein of SARS-CoV-2 is responsible for its binding to angiotensin-converting enzyme 2 (ACE2) receptor. It contains multiple dominant neutralizing epitopes and serves as an important antigen for the development of COVID-19 vaccines. Here, we showed that immunization of mice with a candidate subunit vaccine consisting of SARS-CoV-2 RBD and Fc fragment of human IgG, as an immunopotentiator, elicited high titer of RBD-specific antibodies with robust neutralizing activity against both pseudotyped and live SARS-CoV-2 infections. The mouse antisera could also effectively neutralize infection by pseudotyped SARS-CoV-2 with several natural mutations in RBD and the IgG extracted from the mouse antisera could also show neutralization against pseudotyped SARS-CoV and SARS-related coronavirus (SARSr-CoV). Vaccination of human ACE2 transgenic mice with RBD-Fc could effectively protect mice from the SARS-CoV-2 challenge. These results suggest that SARS-CoV-2 RBD-Fc has good potential to be further developed as an effective and broad-spectrum vaccine to prevent infection of the current SARS-CoV-2 and its mutants, as well as future emerging SARSr-CoVs and re-emerging SARS-CoV. |
doi_str_mv | 10.1038/s41392-020-00402-5 |
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The receptor-binding domain (RBD) in the spike protein of SARS-CoV-2 is responsible for its binding to angiotensin-converting enzyme 2 (ACE2) receptor. It contains multiple dominant neutralizing epitopes and serves as an important antigen for the development of COVID-19 vaccines. Here, we showed that immunization of mice with a candidate subunit vaccine consisting of SARS-CoV-2 RBD and Fc fragment of human IgG, as an immunopotentiator, elicited high titer of RBD-specific antibodies with robust neutralizing activity against both pseudotyped and live SARS-CoV-2 infections. The mouse antisera could also effectively neutralize infection by pseudotyped SARS-CoV-2 with several natural mutations in RBD and the IgG extracted from the mouse antisera could also show neutralization against pseudotyped SARS-CoV and SARS-related coronavirus (SARSr-CoV). Vaccination of human ACE2 transgenic mice with RBD-Fc could effectively protect mice from the SARS-CoV-2 challenge. These results suggest that SARS-CoV-2 RBD-Fc has good potential to be further developed as an effective and broad-spectrum vaccine to prevent infection of the current SARS-CoV-2 and its mutants, as well as future emerging SARSr-CoVs and re-emerging SARS-CoV.</description><identifier>ISSN: 2059-3635</identifier><identifier>ISSN: 2095-9907</identifier><identifier>EISSN: 2059-3635</identifier><identifier>DOI: 10.1038/s41392-020-00402-5</identifier><identifier>PMID: 33247109</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/250/254 ; 631/326/590 ; Angiotensin-Converting Enzyme 2 - antagonists & inhibitors ; Angiotensin-Converting Enzyme 2 - immunology ; Animals ; Antibodies, Neutralizing - immunology ; Antibodies, Neutralizing - pharmacology ; Cancer Research ; Cell Biology ; Coronaviruses ; COVID-19 ; COVID-19 - drug therapy ; COVID-19 - immunology ; COVID-19 - virology ; COVID-19 vaccines ; COVID-19 Vaccines - immunology ; COVID-19 Vaccines - pharmacology ; Epitopes - immunology ; Humans ; Immunoglobulin Fc Fragments - immunology ; Immunoglobulin Fc Fragments - pharmacology ; Internal Medicine ; Medicine ; Medicine & Public Health ; Mice ; Mice, Inbred BALB C ; Oncology ; Pandemics ; Pathology ; Protein Binding - drug effects ; Protein Binding - immunology ; Receptors, Virus - genetics ; Receptors, Virus - immunology ; SARS-CoV-2 - immunology ; SARS-CoV-2 - pathogenicity ; Severe acute respiratory syndrome coronavirus 2 ; Spike Glycoprotein, Coronavirus - antagonists & inhibitors ; Spike Glycoprotein, Coronavirus - immunology</subject><ispartof>Signal transduction and targeted therapy, 2020-11, Vol.5 (1), p.282-282, Article 282</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-87222ca7ba0f21f840e3769c3549adbc958ee3025dd8c8b72bcb0d056422bbf13</citedby><cites>FETCH-LOGICAL-c540t-87222ca7ba0f21f840e3769c3549adbc958ee3025dd8c8b72bcb0d056422bbf13</cites><orcidid>0000-0002-2255-0391 ; 0000-0001-8283-7135</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691975/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691975/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33247109$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Zezhong</creatorcontrib><creatorcontrib>Xu, Wei</creatorcontrib><creatorcontrib>Xia, Shuai</creatorcontrib><creatorcontrib>Gu, Chenjian</creatorcontrib><creatorcontrib>Wang, Xinling</creatorcontrib><creatorcontrib>Wang, Qian</creatorcontrib><creatorcontrib>Zhou, Jie</creatorcontrib><creatorcontrib>Wu, Yanling</creatorcontrib><creatorcontrib>Cai, Xia</creatorcontrib><creatorcontrib>Qu, Di</creatorcontrib><creatorcontrib>Ying, Tianlei</creatorcontrib><creatorcontrib>Xie, Youhua</creatorcontrib><creatorcontrib>Lu, Lu</creatorcontrib><creatorcontrib>Yuan, Zhenghong</creatorcontrib><creatorcontrib>Jiang, Shibo</creatorcontrib><title>RBD-Fc-based COVID-19 vaccine candidate induces highly potent SARS-CoV-2 neutralizing antibody response</title><title>Signal transduction and targeted therapy</title><addtitle>Sig Transduct Target Ther</addtitle><addtitle>Signal Transduct Target Ther</addtitle><description>The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed serious threats to global health and economy, thus calling for the development of safe and effective vaccines. The receptor-binding domain (RBD) in the spike protein of SARS-CoV-2 is responsible for its binding to angiotensin-converting enzyme 2 (ACE2) receptor. It contains multiple dominant neutralizing epitopes and serves as an important antigen for the development of COVID-19 vaccines. Here, we showed that immunization of mice with a candidate subunit vaccine consisting of SARS-CoV-2 RBD and Fc fragment of human IgG, as an immunopotentiator, elicited high titer of RBD-specific antibodies with robust neutralizing activity against both pseudotyped and live SARS-CoV-2 infections. The mouse antisera could also effectively neutralize infection by pseudotyped SARS-CoV-2 with several natural mutations in RBD and the IgG extracted from the mouse antisera could also show neutralization against pseudotyped SARS-CoV and SARS-related coronavirus (SARSr-CoV). Vaccination of human ACE2 transgenic mice with RBD-Fc could effectively protect mice from the SARS-CoV-2 challenge. These results suggest that SARS-CoV-2 RBD-Fc has good potential to be further developed as an effective and broad-spectrum vaccine to prevent infection of the current SARS-CoV-2 and its mutants, as well as future emerging SARSr-CoVs and re-emerging SARS-CoV.</description><subject>631/250/254</subject><subject>631/326/590</subject><subject>Angiotensin-Converting Enzyme 2 - antagonists & inhibitors</subject><subject>Angiotensin-Converting Enzyme 2 - immunology</subject><subject>Animals</subject><subject>Antibodies, Neutralizing - immunology</subject><subject>Antibodies, Neutralizing - pharmacology</subject><subject>Cancer Research</subject><subject>Cell Biology</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>COVID-19 - drug therapy</subject><subject>COVID-19 - immunology</subject><subject>COVID-19 - virology</subject><subject>COVID-19 vaccines</subject><subject>COVID-19 Vaccines - immunology</subject><subject>COVID-19 Vaccines - pharmacology</subject><subject>Epitopes - immunology</subject><subject>Humans</subject><subject>Immunoglobulin Fc Fragments - immunology</subject><subject>Immunoglobulin Fc Fragments - pharmacology</subject><subject>Internal Medicine</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Oncology</subject><subject>Pandemics</subject><subject>Pathology</subject><subject>Protein Binding - drug effects</subject><subject>Protein Binding - immunology</subject><subject>Receptors, Virus - genetics</subject><subject>Receptors, Virus - immunology</subject><subject>SARS-CoV-2 - immunology</subject><subject>SARS-CoV-2 - pathogenicity</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Spike Glycoprotein, Coronavirus - antagonists & inhibitors</subject><subject>Spike Glycoprotein, Coronavirus - immunology</subject><issn>2059-3635</issn><issn>2095-9907</issn><issn>2059-3635</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kU1P3DAQhqOqqCDKH-ihstRLL27tsR0nl0p0KR8SEhJQrpa_kjXK2ts4QVp-fU2XUsqB04w0z7zzjt6q-kDJF0pY8zVzylrABAgmhBPA4k21B0S0mNVMvH3W71YHOd8SQmjNpBT8XbXLGHBJSbtX9Zffj_CxxUZn79Di4ubsCNMW3WlrQ_TI6uiC05NHIbrZ-oyWoV8OG7ROk48Tujq8vMKLdIMBRT9Pox7CfYg90nEKJrkNGn1ep5j9-2qn00P2B491v_p5_ON6cYrPL07OFofn2ApOJtxIALBaGk06oF3DiWeybi0TvNXO2FY03jMCwrnGNkaCsYY4ImoOYExH2X71bau7ns3KO1tMFlNqPYaVHjcq6aD-n8SwVH26U-UKbaUoAp8fBcb0a_Z5UquQrR8GHX2aswJeC84EAyjopxfobZrHWN4rlGRQy7rhhYItZceU8-i7JzOUqIco1TZKVaJUf6JUDy4-Pn_jaeVvcAVgWyCXUez9-O_2K7K_ASocqJo</recordid><startdate>20201127</startdate><enddate>20201127</enddate><creator>Liu, Zezhong</creator><creator>Xu, Wei</creator><creator>Xia, Shuai</creator><creator>Gu, Chenjian</creator><creator>Wang, Xinling</creator><creator>Wang, Qian</creator><creator>Zhou, Jie</creator><creator>Wu, Yanling</creator><creator>Cai, Xia</creator><creator>Qu, Di</creator><creator>Ying, Tianlei</creator><creator>Xie, Youhua</creator><creator>Lu, Lu</creator><creator>Yuan, Zhenghong</creator><creator>Jiang, Shibo</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>COVID</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2255-0391</orcidid><orcidid>https://orcid.org/0000-0001-8283-7135</orcidid></search><sort><creationdate>20201127</creationdate><title>RBD-Fc-based COVID-19 vaccine candidate induces highly potent SARS-CoV-2 neutralizing antibody response</title><author>Liu, Zezhong ; Xu, Wei ; Xia, Shuai ; Gu, Chenjian ; Wang, Xinling ; Wang, Qian ; Zhou, Jie ; Wu, Yanling ; Cai, Xia ; Qu, Di ; Ying, Tianlei ; Xie, Youhua ; Lu, Lu ; Yuan, Zhenghong ; Jiang, Shibo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c540t-87222ca7ba0f21f840e3769c3549adbc958ee3025dd8c8b72bcb0d056422bbf13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>631/250/254</topic><topic>631/326/590</topic><topic>Angiotensin-Converting Enzyme 2 - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Signal transduction and targeted therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Zezhong</au><au>Xu, Wei</au><au>Xia, Shuai</au><au>Gu, Chenjian</au><au>Wang, Xinling</au><au>Wang, Qian</au><au>Zhou, Jie</au><au>Wu, Yanling</au><au>Cai, Xia</au><au>Qu, Di</au><au>Ying, Tianlei</au><au>Xie, Youhua</au><au>Lu, Lu</au><au>Yuan, Zhenghong</au><au>Jiang, Shibo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>RBD-Fc-based COVID-19 vaccine candidate induces highly potent SARS-CoV-2 neutralizing antibody response</atitle><jtitle>Signal transduction and targeted therapy</jtitle><stitle>Sig Transduct Target Ther</stitle><addtitle>Signal Transduct Target Ther</addtitle><date>2020-11-27</date><risdate>2020</risdate><volume>5</volume><issue>1</issue><spage>282</spage><epage>282</epage><pages>282-282</pages><artnum>282</artnum><issn>2059-3635</issn><issn>2095-9907</issn><eissn>2059-3635</eissn><abstract>The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed serious threats to global health and economy, thus calling for the development of safe and effective vaccines. The receptor-binding domain (RBD) in the spike protein of SARS-CoV-2 is responsible for its binding to angiotensin-converting enzyme 2 (ACE2) receptor. It contains multiple dominant neutralizing epitopes and serves as an important antigen for the development of COVID-19 vaccines. Here, we showed that immunization of mice with a candidate subunit vaccine consisting of SARS-CoV-2 RBD and Fc fragment of human IgG, as an immunopotentiator, elicited high titer of RBD-specific antibodies with robust neutralizing activity against both pseudotyped and live SARS-CoV-2 infections. The mouse antisera could also effectively neutralize infection by pseudotyped SARS-CoV-2 with several natural mutations in RBD and the IgG extracted from the mouse antisera could also show neutralization against pseudotyped SARS-CoV and SARS-related coronavirus (SARSr-CoV). Vaccination of human ACE2 transgenic mice with RBD-Fc could effectively protect mice from the SARS-CoV-2 challenge. These results suggest that SARS-CoV-2 RBD-Fc has good potential to be further developed as an effective and broad-spectrum vaccine to prevent infection of the current SARS-CoV-2 and its mutants, as well as future emerging SARSr-CoVs and re-emerging SARS-CoV.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>33247109</pmid><doi>10.1038/s41392-020-00402-5</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-2255-0391</orcidid><orcidid>https://orcid.org/0000-0001-8283-7135</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | 631/250/254 631/326/590 Angiotensin-Converting Enzyme 2 - antagonists & inhibitors Angiotensin-Converting Enzyme 2 - immunology Animals Antibodies, Neutralizing - immunology Antibodies, Neutralizing - pharmacology Cancer Research Cell Biology Coronaviruses COVID-19 COVID-19 - drug therapy COVID-19 - immunology COVID-19 - virology COVID-19 vaccines COVID-19 Vaccines - immunology COVID-19 Vaccines - pharmacology Epitopes - immunology Humans Immunoglobulin Fc Fragments - immunology Immunoglobulin Fc Fragments - pharmacology Internal Medicine Medicine Medicine & Public Health Mice Mice, Inbred BALB C Oncology Pandemics Pathology Protein Binding - drug effects Protein Binding - immunology Receptors, Virus - genetics Receptors, Virus - immunology SARS-CoV-2 - immunology SARS-CoV-2 - pathogenicity Severe acute respiratory syndrome coronavirus 2 Spike Glycoprotein, Coronavirus - antagonists & inhibitors Spike Glycoprotein, Coronavirus - immunology |
title | RBD-Fc-based COVID-19 vaccine candidate induces highly potent SARS-CoV-2 neutralizing antibody response |
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