A Fc-enhanced NTD-binding non-neutralizing antibody delays virus spread and synergizes with a nAb to protect mice from lethal SARS-CoV-2 infection
Emerging evidence indicates that both neutralizing and Fc-mediated effector functions of antibodies contribute to protection against SARS-CoV-2. It is unclear whether Fc-effector functions alone can protect against SARS-CoV-2. Here, we isolated CV3-13, a non-neutralizing antibody, from a convalescen...
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| Veröffentlicht in: | Cell reports (Cambridge) 2022-02, Vol.38 (7), p.110368-110368, Article 110368 |
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| creator | Beaudoin-Bussières, Guillaume Chen, Yaozong Ullah, Irfan Prévost, Jérémie Tolbert, William D. Symmes, Kelly Ding, Shilei Benlarbi, Mehdi Gong, Shang Yu Tauzin, Alexandra Gasser, Romain Chatterjee, Debashree Vézina, Dani Goyette, Guillaume Richard, Jonathan Zhou, Fei Stamatatos, Leonidas McGuire, Andrew T. Charest, Hughes Roger, Michel Pozharski, Edwin Kumar, Priti Mothes, Walther Uchil, Pradeep D. Pazgier, Marzena Finzi, Andrés |
| description | Emerging evidence indicates that both neutralizing and Fc-mediated effector functions of antibodies contribute to protection against SARS-CoV-2. It is unclear whether Fc-effector functions alone can protect against SARS-CoV-2. Here, we isolated CV3-13, a non-neutralizing antibody, from a convalescent individual with potent Fc-mediated effector functions. The cryoelectron microscopy structure of CV3-13 in complex with the SARS-CoV-2 spike reveals that the antibody binds from a distinct angle of approach to an N-terminal domain (NTD) epitope that only partially overlaps with the NTD supersite recognized by neutralizing antibodies. CV3-13 does not alter the replication dynamics of SARS-CoV-2 in K18-hACE2 mice, but its Fc-enhanced version significantly delays virus spread, neuroinvasion, and death in prophylactic settings. Interestingly, the combination of Fc-enhanced non-neutralizing CV3-13 with Fc-compromised neutralizing CV3-25 completely protects mice from lethal SARS-CoV-2 infection. Altogether, our data demonstrate that efficient Fc-mediated effector functions can potently contribute to the in vivo efficacy of anti-SARS-CoV-2 antibodies.
[Display omitted]
•Non-neutralizing antibody CV3-13 binds an epitope in NTD of SARS-CoV-2 spike•CV3-13 has a unique angle of approach and mediates potent Fc-effector functions•Fc-enhanced CV3-13 delays virus spread and death in SARS-CoV-2-challenged mice•Fc-enhanced CV3-13 synergizes with Fc-compromised nAb to protect 100% of the mice
The in vivo impact of non-nAbs on SARS-CoV-2 infection is unclear. Here, Beaudoin-Bussières et al. show that a Fc-enhanced version of non-nAb CV3-13 delays SARS-CoV-2 spread and death in mice. Fc-enhanced CV3-13 combined with a Fc-compromised nAb synergizes to protect mice, revealing the importance of non-nAbs during SARS-CoV-2 infection. |
| doi_str_mv | 10.1016/j.celrep.2022.110368 |
| format | Article |
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[Display omitted]
•Non-neutralizing antibody CV3-13 binds an epitope in NTD of SARS-CoV-2 spike•CV3-13 has a unique angle of approach and mediates potent Fc-effector functions•Fc-enhanced CV3-13 delays virus spread and death in SARS-CoV-2-challenged mice•Fc-enhanced CV3-13 synergizes with Fc-compromised nAb to protect 100% of the mice
The in vivo impact of non-nAbs on SARS-CoV-2 infection is unclear. Here, Beaudoin-Bussières et al. show that a Fc-enhanced version of non-nAb CV3-13 delays SARS-CoV-2 spread and death in mice. Fc-enhanced CV3-13 combined with a Fc-compromised nAb synergizes to protect mice, revealing the importance of non-nAbs during SARS-CoV-2 infection.</description><identifier>ISSN: 2211-1247</identifier><identifier>EISSN: 2211-1247</identifier><identifier>DOI: 10.1016/j.celrep.2022.110368</identifier><identifier>PMID: 35123652</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>ADCC ; Animals ; Antibodies, Neutralizing - therapeutic use ; Antibodies, Viral - chemistry ; Antibodies, Viral - immunology ; Antibodies, Viral - therapeutic use ; Antibody-Dependent Cell Cytotoxicity ; coronavirus ; COVID-19 ; COVID-19 - mortality ; COVID-19 - prevention & control ; COVID-19 - therapy ; COVID-19 - transmission ; Disease Models, Animal ; Epitopes ; Fc-effector functions ; Humans ; Immunization, Passive - mortality ; Immunoglobulin Fab Fragments - chemistry ; Immunoglobulin Fab Fragments - metabolism ; Immunoglobulin Fc Fragments - genetics ; Immunoglobulin Fc Fragments - immunology ; K18-hACE2 mice ; Mice ; non-neutralizing antibodies ; Protein Binding ; Protein Conformation ; SARS-CoV-2 ; SARS-CoV-2 - immunology ; SARS-CoV-2 - pathogenicity ; spike ; Spike Glycoprotein, Coronavirus - chemistry ; Spike Glycoprotein, Coronavirus - immunology ; Spike Glycoprotein, Coronavirus - metabolism ; synergy</subject><ispartof>Cell reports (Cambridge), 2022-02, Vol.38 (7), p.110368-110368, Article 110368</ispartof><rights>2022</rights><rights>Copyright © 2022. Published by Elsevier Inc.</rights><rights>2022. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c463t-9b9b7632962ff19f805c0f4fcbe95370a5495d899faf80bbb4b8ddc173e7e8c93</citedby><cites>FETCH-LOGICAL-c463t-9b9b7632962ff19f805c0f4fcbe95370a5495d899faf80bbb4b8ddc173e7e8c93</cites><orcidid>0000-0002-6901-5601 ; 0000-0003-3277-568X ; 0000-0001-9966-3784 ; 0000-0001-5380-2339 ; 0000-0002-4442-8442 ; 0000-0003-0594-5057 ; 0000-0001-9153-3600 ; 0000-0001-8211-6207 ; 0000-0002-1106-7097 ; 0000-0002-7760-8693 ; 0000-0002-8565-1106 ; 0000-0002-7236-858X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,864,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35123652$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Beaudoin-Bussières, Guillaume</creatorcontrib><creatorcontrib>Chen, Yaozong</creatorcontrib><creatorcontrib>Ullah, Irfan</creatorcontrib><creatorcontrib>Prévost, Jérémie</creatorcontrib><creatorcontrib>Tolbert, William D.</creatorcontrib><creatorcontrib>Symmes, Kelly</creatorcontrib><creatorcontrib>Ding, Shilei</creatorcontrib><creatorcontrib>Benlarbi, Mehdi</creatorcontrib><creatorcontrib>Gong, Shang Yu</creatorcontrib><creatorcontrib>Tauzin, Alexandra</creatorcontrib><creatorcontrib>Gasser, Romain</creatorcontrib><creatorcontrib>Chatterjee, Debashree</creatorcontrib><creatorcontrib>Vézina, Dani</creatorcontrib><creatorcontrib>Goyette, Guillaume</creatorcontrib><creatorcontrib>Richard, Jonathan</creatorcontrib><creatorcontrib>Zhou, Fei</creatorcontrib><creatorcontrib>Stamatatos, Leonidas</creatorcontrib><creatorcontrib>McGuire, Andrew T.</creatorcontrib><creatorcontrib>Charest, Hughes</creatorcontrib><creatorcontrib>Roger, Michel</creatorcontrib><creatorcontrib>Pozharski, Edwin</creatorcontrib><creatorcontrib>Kumar, Priti</creatorcontrib><creatorcontrib>Mothes, Walther</creatorcontrib><creatorcontrib>Uchil, Pradeep D.</creatorcontrib><creatorcontrib>Pazgier, Marzena</creatorcontrib><creatorcontrib>Finzi, Andrés</creatorcontrib><title>A Fc-enhanced NTD-binding non-neutralizing antibody delays virus spread and synergizes with a nAb to protect mice from lethal SARS-CoV-2 infection</title><title>Cell reports (Cambridge)</title><addtitle>Cell Rep</addtitle><description>Emerging evidence indicates that both neutralizing and Fc-mediated effector functions of antibodies contribute to protection against SARS-CoV-2. It is unclear whether Fc-effector functions alone can protect against SARS-CoV-2. Here, we isolated CV3-13, a non-neutralizing antibody, from a convalescent individual with potent Fc-mediated effector functions. The cryoelectron microscopy structure of CV3-13 in complex with the SARS-CoV-2 spike reveals that the antibody binds from a distinct angle of approach to an N-terminal domain (NTD) epitope that only partially overlaps with the NTD supersite recognized by neutralizing antibodies. CV3-13 does not alter the replication dynamics of SARS-CoV-2 in K18-hACE2 mice, but its Fc-enhanced version significantly delays virus spread, neuroinvasion, and death in prophylactic settings. Interestingly, the combination of Fc-enhanced non-neutralizing CV3-13 with Fc-compromised neutralizing CV3-25 completely protects mice from lethal SARS-CoV-2 infection. Altogether, our data demonstrate that efficient Fc-mediated effector functions can potently contribute to the in vivo efficacy of anti-SARS-CoV-2 antibodies.
[Display omitted]
•Non-neutralizing antibody CV3-13 binds an epitope in NTD of SARS-CoV-2 spike•CV3-13 has a unique angle of approach and mediates potent Fc-effector functions•Fc-enhanced CV3-13 delays virus spread and death in SARS-CoV-2-challenged mice•Fc-enhanced CV3-13 synergizes with Fc-compromised nAb to protect 100% of the mice
The in vivo impact of non-nAbs on SARS-CoV-2 infection is unclear. Here, Beaudoin-Bussières et al. show that a Fc-enhanced version of non-nAb CV3-13 delays SARS-CoV-2 spread and death in mice. Fc-enhanced CV3-13 combined with a Fc-compromised nAb synergizes to protect mice, revealing the importance of non-nAbs during SARS-CoV-2 infection.</description><subject>ADCC</subject><subject>Animals</subject><subject>Antibodies, Neutralizing - therapeutic use</subject><subject>Antibodies, Viral - chemistry</subject><subject>Antibodies, Viral - immunology</subject><subject>Antibodies, Viral - therapeutic use</subject><subject>Antibody-Dependent Cell Cytotoxicity</subject><subject>coronavirus</subject><subject>COVID-19</subject><subject>COVID-19 - mortality</subject><subject>COVID-19 - prevention & control</subject><subject>COVID-19 - therapy</subject><subject>COVID-19 - transmission</subject><subject>Disease Models, Animal</subject><subject>Epitopes</subject><subject>Fc-effector functions</subject><subject>Humans</subject><subject>Immunization, Passive - mortality</subject><subject>Immunoglobulin Fab Fragments - chemistry</subject><subject>Immunoglobulin Fab Fragments - metabolism</subject><subject>Immunoglobulin Fc Fragments - genetics</subject><subject>Immunoglobulin Fc Fragments - immunology</subject><subject>K18-hACE2 mice</subject><subject>Mice</subject><subject>non-neutralizing antibodies</subject><subject>Protein Binding</subject><subject>Protein Conformation</subject><subject>SARS-CoV-2</subject><subject>SARS-CoV-2 - immunology</subject><subject>SARS-CoV-2 - pathogenicity</subject><subject>spike</subject><subject>Spike Glycoprotein, Coronavirus - chemistry</subject><subject>Spike Glycoprotein, Coronavirus - immunology</subject><subject>Spike Glycoprotein, Coronavirus - metabolism</subject><subject>synergy</subject><issn>2211-1247</issn><issn>2211-1247</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1vEzEQhlcIRKvSf4CQj1w22N5PX5CiQAGpAokWrpY_xomjXXuxvUHpz-AX41VKKRfsgy3POzOe9ymKlwSvCCbtm_1KwRBgWlFM6YoQXLX9k-KcUkJKQuvu6aP7WXEZ4x7n1WJCWP28OKsaQqu2oefFrzW6UiW4nXAKNPp8-66U1mnrtsh5VzqYUxCDvVsehEtWen1EGgZxjOhgwxxRnAIInYMaxaODsLV3ENFPm3ZIILeWKHk0BZ9AJTRaBcgEP6IB0k4M6Gb99abc-O8lRdaZLLHevSieGTFEuLw_L4pvV-9vNx_L6y8fPm3W16Wq2yqVTDLZtRVlLTWGMNPjRmFTGyWBNVWHRVOzRveMGZFjUspa9lor0lXQQa9YdVG8PdWdZjmCVuCWUfkU7CjCkXth-b8RZ3d86w-87_o2m5cLvL4vEPyPGWLio42ZyyAc-Dly2uZNaVfXWVqfpCr4GAOYhzYE84Uo3_MTUb4Q5SeiOe3V4y8-JP3h93cGyEYdLAQelYUFpQ3ZTa69_X-H37Kztik</recordid><startdate>20220215</startdate><enddate>20220215</enddate><creator>Beaudoin-Bussières, Guillaume</creator><creator>Chen, Yaozong</creator><creator>Ullah, Irfan</creator><creator>Prévost, Jérémie</creator><creator>Tolbert, William D.</creator><creator>Symmes, Kelly</creator><creator>Ding, Shilei</creator><creator>Benlarbi, Mehdi</creator><creator>Gong, Shang Yu</creator><creator>Tauzin, Alexandra</creator><creator>Gasser, Romain</creator><creator>Chatterjee, Debashree</creator><creator>Vézina, Dani</creator><creator>Goyette, Guillaume</creator><creator>Richard, Jonathan</creator><creator>Zhou, Fei</creator><creator>Stamatatos, Leonidas</creator><creator>McGuire, Andrew T.</creator><creator>Charest, Hughes</creator><creator>Roger, Michel</creator><creator>Pozharski, Edwin</creator><creator>Kumar, Priti</creator><creator>Mothes, Walther</creator><creator>Uchil, Pradeep D.</creator><creator>Pazgier, Marzena</creator><creator>Finzi, Andrés</creator><general>Elsevier Inc</general><general>Cell Press</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-6901-5601</orcidid><orcidid>https://orcid.org/0000-0003-3277-568X</orcidid><orcidid>https://orcid.org/0000-0001-9966-3784</orcidid><orcidid>https://orcid.org/0000-0001-5380-2339</orcidid><orcidid>https://orcid.org/0000-0002-4442-8442</orcidid><orcidid>https://orcid.org/0000-0003-0594-5057</orcidid><orcidid>https://orcid.org/0000-0001-9153-3600</orcidid><orcidid>https://orcid.org/0000-0001-8211-6207</orcidid><orcidid>https://orcid.org/0000-0002-1106-7097</orcidid><orcidid>https://orcid.org/0000-0002-7760-8693</orcidid><orcidid>https://orcid.org/0000-0002-8565-1106</orcidid><orcidid>https://orcid.org/0000-0002-7236-858X</orcidid></search><sort><creationdate>20220215</creationdate><title>A Fc-enhanced NTD-binding non-neutralizing antibody delays virus spread and synergizes with a nAb to protect mice from lethal SARS-CoV-2 infection</title><author>Beaudoin-Bussières, Guillaume ; Chen, Yaozong ; Ullah, Irfan ; Prévost, Jérémie ; Tolbert, William D. ; Symmes, Kelly ; Ding, Shilei ; Benlarbi, Mehdi ; Gong, Shang Yu ; Tauzin, Alexandra ; Gasser, Romain ; Chatterjee, Debashree ; Vézina, Dani ; Goyette, Guillaume ; Richard, Jonathan ; Zhou, Fei ; Stamatatos, Leonidas ; McGuire, Andrew T. ; Charest, Hughes ; Roger, Michel ; Pozharski, Edwin ; Kumar, Priti ; Mothes, Walther ; Uchil, Pradeep D. ; Pazgier, Marzena ; Finzi, Andrés</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c463t-9b9b7632962ff19f805c0f4fcbe95370a5495d899faf80bbb4b8ddc173e7e8c93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>ADCC</topic><topic>Animals</topic><topic>Antibodies, Neutralizing - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell reports (Cambridge)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Beaudoin-Bussières, Guillaume</au><au>Chen, Yaozong</au><au>Ullah, Irfan</au><au>Prévost, Jérémie</au><au>Tolbert, William D.</au><au>Symmes, Kelly</au><au>Ding, Shilei</au><au>Benlarbi, Mehdi</au><au>Gong, Shang Yu</au><au>Tauzin, Alexandra</au><au>Gasser, Romain</au><au>Chatterjee, Debashree</au><au>Vézina, Dani</au><au>Goyette, Guillaume</au><au>Richard, Jonathan</au><au>Zhou, Fei</au><au>Stamatatos, Leonidas</au><au>McGuire, Andrew T.</au><au>Charest, Hughes</au><au>Roger, Michel</au><au>Pozharski, Edwin</au><au>Kumar, Priti</au><au>Mothes, Walther</au><au>Uchil, Pradeep D.</au><au>Pazgier, Marzena</au><au>Finzi, Andrés</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Fc-enhanced NTD-binding non-neutralizing antibody delays virus spread and synergizes with a nAb to protect mice from lethal SARS-CoV-2 infection</atitle><jtitle>Cell reports (Cambridge)</jtitle><addtitle>Cell Rep</addtitle><date>2022-02-15</date><risdate>2022</risdate><volume>38</volume><issue>7</issue><spage>110368</spage><epage>110368</epage><pages>110368-110368</pages><artnum>110368</artnum><issn>2211-1247</issn><eissn>2211-1247</eissn><abstract>Emerging evidence indicates that both neutralizing and Fc-mediated effector functions of antibodies contribute to protection against SARS-CoV-2. It is unclear whether Fc-effector functions alone can protect against SARS-CoV-2. Here, we isolated CV3-13, a non-neutralizing antibody, from a convalescent individual with potent Fc-mediated effector functions. The cryoelectron microscopy structure of CV3-13 in complex with the SARS-CoV-2 spike reveals that the antibody binds from a distinct angle of approach to an N-terminal domain (NTD) epitope that only partially overlaps with the NTD supersite recognized by neutralizing antibodies. CV3-13 does not alter the replication dynamics of SARS-CoV-2 in K18-hACE2 mice, but its Fc-enhanced version significantly delays virus spread, neuroinvasion, and death in prophylactic settings. Interestingly, the combination of Fc-enhanced non-neutralizing CV3-13 with Fc-compromised neutralizing CV3-25 completely protects mice from lethal SARS-CoV-2 infection. Altogether, our data demonstrate that efficient Fc-mediated effector functions can potently contribute to the in vivo efficacy of anti-SARS-CoV-2 antibodies.
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•Non-neutralizing antibody CV3-13 binds an epitope in NTD of SARS-CoV-2 spike•CV3-13 has a unique angle of approach and mediates potent Fc-effector functions•Fc-enhanced CV3-13 delays virus spread and death in SARS-CoV-2-challenged mice•Fc-enhanced CV3-13 synergizes with Fc-compromised nAb to protect 100% of the mice
The in vivo impact of non-nAbs on SARS-CoV-2 infection is unclear. Here, Beaudoin-Bussières et al. show that a Fc-enhanced version of non-nAb CV3-13 delays SARS-CoV-2 spread and death in mice. Fc-enhanced CV3-13 combined with a Fc-compromised nAb synergizes to protect mice, revealing the importance of non-nAbs during SARS-CoV-2 infection.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>35123652</pmid><doi>10.1016/j.celrep.2022.110368</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-6901-5601</orcidid><orcidid>https://orcid.org/0000-0003-3277-568X</orcidid><orcidid>https://orcid.org/0000-0001-9966-3784</orcidid><orcidid>https://orcid.org/0000-0001-5380-2339</orcidid><orcidid>https://orcid.org/0000-0002-4442-8442</orcidid><orcidid>https://orcid.org/0000-0003-0594-5057</orcidid><orcidid>https://orcid.org/0000-0001-9153-3600</orcidid><orcidid>https://orcid.org/0000-0001-8211-6207</orcidid><orcidid>https://orcid.org/0000-0002-1106-7097</orcidid><orcidid>https://orcid.org/0000-0002-7760-8693</orcidid><orcidid>https://orcid.org/0000-0002-8565-1106</orcidid><orcidid>https://orcid.org/0000-0002-7236-858X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2211-1247 |
| ispartof | Cell reports (Cambridge), 2022-02, Vol.38 (7), p.110368-110368, Article 110368 |
| issn | 2211-1247 2211-1247 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8786652 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Cell Press Free Archives; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | ADCC Animals Antibodies, Neutralizing - therapeutic use Antibodies, Viral - chemistry Antibodies, Viral - immunology Antibodies, Viral - therapeutic use Antibody-Dependent Cell Cytotoxicity coronavirus COVID-19 COVID-19 - mortality COVID-19 - prevention & control COVID-19 - therapy COVID-19 - transmission Disease Models, Animal Epitopes Fc-effector functions Humans Immunization, Passive - mortality Immunoglobulin Fab Fragments - chemistry Immunoglobulin Fab Fragments - metabolism Immunoglobulin Fc Fragments - genetics Immunoglobulin Fc Fragments - immunology K18-hACE2 mice Mice non-neutralizing antibodies Protein Binding Protein Conformation SARS-CoV-2 SARS-CoV-2 - immunology SARS-CoV-2 - pathogenicity spike Spike Glycoprotein, Coronavirus - chemistry Spike Glycoprotein, Coronavirus - immunology Spike Glycoprotein, Coronavirus - metabolism synergy |
| title | A Fc-enhanced NTD-binding non-neutralizing antibody delays virus spread and synergizes with a nAb to protect mice from lethal SARS-CoV-2 infection |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-01T20%3A38%3A15IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20Fc-enhanced%20NTD-binding%20non-neutralizing%20antibody%20delays%20virus%20spread%20and%20synergizes%20with%20a%20nAb%20to%20protect%20mice%20from%20lethal%20SARS-CoV-2%20infection&rft.jtitle=Cell%20reports%20(Cambridge)&rft.au=Beaudoin-Bussi%C3%A8res,%20Guillaume&rft.date=2022-02-15&rft.volume=38&rft.issue=7&rft.spage=110368&rft.epage=110368&rft.pages=110368-110368&rft.artnum=110368&rft.issn=2211-1247&rft.eissn=2211-1247&rft_id=info:doi/10.1016/j.celrep.2022.110368&rft_dat=%3Cproquest_pubme%3E2626222744%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2626222744&rft_id=info:pmid/35123652&rft_els_id=S2211124722000894&rfr_iscdi=true |