In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies
SARS-CoV-2-neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor-binding domain (RBD) or the N-terminal domain (NTD) of SARS-CoV-2 spike from individuals with acute o...
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| Vydáno v: | Cell Ročník 184; číslo 16; s. 4203 |
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| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
United States
05.08.2021
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| ISSN: | 1097-4172, 1097-4172 |
| On-line přístup: | Zjistit podrobnosti o přístupu |
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| Abstract | SARS-CoV-2-neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor-binding domain (RBD) or the N-terminal domain (NTD) of SARS-CoV-2 spike from individuals with acute or convalescent SARS-CoV-2 or a history of SARS-CoV infection. Cryo-electron microscopy of RBD and NTD antibodies demonstrated function-specific modes of binding. Select RBD NAbs also demonstrated Fc receptor-γ (FcγR)-mediated enhancement of virus infection in vitro, while five non-neutralizing NTD antibodies mediated FcγR-independent in vitro infection enhancement. However, both types of infection-enhancing antibodies protected from SARS-CoV-2 replication in monkeys and mice. Three of 46 monkeys infused with enhancing antibodies had higher lung inflammation scores compared to controls. One monkey had alveolar edema and elevated bronchoalveolar lavage inflammatory cytokines. Thus, while in vitro antibody-enhanced infection does not necessarily herald enhanced infection in vivo, increased lung inflammation can rarely occur in SARS-CoV-2 antibody-infused macaques. |
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| AbstractList | SARS-CoV-2-neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor-binding domain (RBD) or the N-terminal domain (NTD) of SARS-CoV-2 spike from individuals with acute or convalescent SARS-CoV-2 or a history of SARS-CoV infection. Cryo-electron microscopy of RBD and NTD antibodies demonstrated function-specific modes of binding. Select RBD NAbs also demonstrated Fc receptor-γ (FcγR)-mediated enhancement of virus infection in vitro, while five non-neutralizing NTD antibodies mediated FcγR-independent in vitro infection enhancement. However, both types of infection-enhancing antibodies protected from SARS-CoV-2 replication in monkeys and mice. Three of 46 monkeys infused with enhancing antibodies had higher lung inflammation scores compared to controls. One monkey had alveolar edema and elevated bronchoalveolar lavage inflammatory cytokines. Thus, while in vitro antibody-enhanced infection does not necessarily herald enhanced infection in vivo, increased lung inflammation can rarely occur in SARS-CoV-2 antibody-infused macaques. SARS-CoV-2-neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor-binding domain (RBD) or the N-terminal domain (NTD) of SARS-CoV-2 spike from individuals with acute or convalescent SARS-CoV-2 or a history of SARS-CoV infection. Cryo-electron microscopy of RBD and NTD antibodies demonstrated function-specific modes of binding. Select RBD NAbs also demonstrated Fc receptor-γ (FcγR)-mediated enhancement of virus infection in vitro, while five non-neutralizing NTD antibodies mediated FcγR-independent in vitro infection enhancement. However, both types of infection-enhancing antibodies protected from SARS-CoV-2 replication in monkeys and mice. Three of 46 monkeys infused with enhancing antibodies had higher lung inflammation scores compared to controls. One monkey had alveolar edema and elevated bronchoalveolar lavage inflammatory cytokines. Thus, while in vitro antibody-enhanced infection does not necessarily herald enhanced infection in vivo, increased lung inflammation can rarely occur in SARS-CoV-2 antibody-infused macaques.SARS-CoV-2-neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor-binding domain (RBD) or the N-terminal domain (NTD) of SARS-CoV-2 spike from individuals with acute or convalescent SARS-CoV-2 or a history of SARS-CoV infection. Cryo-electron microscopy of RBD and NTD antibodies demonstrated function-specific modes of binding. Select RBD NAbs also demonstrated Fc receptor-γ (FcγR)-mediated enhancement of virus infection in vitro, while five non-neutralizing NTD antibodies mediated FcγR-independent in vitro infection enhancement. However, both types of infection-enhancing antibodies protected from SARS-CoV-2 replication in monkeys and mice. Three of 46 monkeys infused with enhancing antibodies had higher lung inflammation scores compared to controls. One monkey had alveolar edema and elevated bronchoalveolar lavage inflammatory cytokines. Thus, while in vitro antibody-enhanced infection does not necessarily herald enhanced infection in vivo, increased lung inflammation can rarely occur in SARS-CoV-2 antibody-infused macaques. |
| Author | Schmidt, Aaron G Gee-Lai, Victoria Foulger, Andrew Parks, Robert Hernandez, Giovanna E Macintyre, Andrew N Haynes, Barton F Sanzone, Aja Caradonna, Timothy M Mascola, John R Barr, Maggie Denny, Thomas N Graham, Barney S Cronin, Kenneth Hauser, Blake M DeMarco, C Todd Minai, Mahnaz Stalls, Victoria Schäfer, Alexandra Saunders, Kevin O Oguin, 3rd, Thomas H Acharya, Priyamvada Feldman, Jared Lu, Xiaozhi Martinez, David R Sutherland, Laura L Moore, Ian N Manne, Kartik Jiang, Chuancang Wang, Yunfei Petzold, Elizabeth W Zhou, Tongqing Alam, S Munir Bock, Kevin W Tse, Longping V Wiehe, Kevin Montefiori, David C Edwards, Robert J Cain, Derek W Kwong, Peter D Kopp, Megan Stover, Erica Scobey, Trevor D Mansouri, Katayoun Janowska, Katarzyna Deyton, Margaret McDanal, Charlene Woods, Christopher W Moody, M Anthony Teng, I-Ting Cai, Fangping Sempowski, Gregory D Nagata, Bianca M Lewis, Mark G Tilahun, Kedamawit Lee, Esther Andersen, Hanne Perez, Lautaro G Von Holle, Tarra Baric, Ralph S Li, Dapeng Gobeil, Sophie M C Seder, Robert Rountree, Wes |
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Electronic address: barton.haynes@duke.edu – sequence: 64 givenname: Kevin O surname: Saunders fullname: Saunders, Kevin O email: kevin.saunders@duke.edu organization: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Surgery, Duke University, Durham, NC 27710, USA; Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: kevin.saunders@duke.edu |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/34242577$$D View this record in MEDLINE/PubMed |
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| Keywords | COVID-19 electron micrograph SARS-CoV-2 cross-neutralization receptor-binding domain neutralizing antibody N-terminal domain antibody-dependent enhancement infection enhancement in vivo protection |
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| SubjectTerms | Animals Antibodies, Neutralizing - immunology Antibodies, Viral - immunology Bronchoalveolar Lavage Fluid - chemistry COVID-19 - pathology COVID-19 - virology Cytokines - metabolism Female Haplorhini Humans Lung - pathology Lung - virology Male Mice Mice, Inbred BALB C Protein Domains Receptors, IgG - metabolism SARS-CoV-2 - isolation & purification SARS-CoV-2 - physiology Spike Glycoprotein, Coronavirus - chemistry Spike Glycoprotein, Coronavirus - immunology Viral Load Virus Replication |
| Title | In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies |
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