Neutralizing and enhancing monoclonal antibodies in SARS-CoV-2 convalescent patients: lessons from early variant infection and impact on shaping emerging variants
Serological studies of COVID-19 convalescent patients have identified polyclonal lineage-specific and cross-reactive antibodies (Abs), with varying effector functions against virus variants. Individual specificities of anti-SARS-CoV-2 Abs and their impact on infectivity by other variants have been l...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2024.2307510 |
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| author | Frédéric Coutant Franck Touret Jean-Jacques Pin Marina Alonzo Cécile Baronti Sandie Munier Mikaël Attia Xavier de Lamballerie Tristan Ferry Pierre Miossec |
| author_facet | Frédéric Coutant Franck Touret Jean-Jacques Pin Marina Alonzo Cécile Baronti Sandie Munier Mikaël Attia Xavier de Lamballerie Tristan Ferry Pierre Miossec |
| author_sort | Frédéric Coutant |
| collection | DOAJ |
| description | Serological studies of COVID-19 convalescent patients have identified polyclonal lineage-specific and cross-reactive antibodies (Abs), with varying effector functions against virus variants. Individual specificities of anti-SARS-CoV-2 Abs and their impact on infectivity by other variants have been little investigated to date. Here, we dissected at a monoclonal level neutralizing and enhancing Abs elicited by early variants and how they affect infectivity of emerging variants. B cells from 13 convalescent patients originally infected by D614G or Alpha variants were immortalized to isolate 445 naturally-produced anti-SARS-CoV-2 Abs. Monoclonal antibodies (mAbs) were tested for their abilities to impact the cytopathic effect of D614G, Delta, and Omicron (BA.1) variants. Ninety-eight exhibited robust neutralization against at least one of the three variant types, while 309 showed minimal or no impact on infectivity. Thirty-eight mAbs enhanced infectivity of SARS-CoV-2. Infection with D614G/Alpha variants generated variant-specific (65 neutralizing Abs, 35 enhancing Abs) and cross-reactive (18 neutralizing Abs, 3 enhancing Abs) mAbs. Interestingly, among the neutralizing mAbs with cross-reactivity restricted to two of the three variants tested, none demonstrated specific neutralization of the Delta and Omicron variants. In contrast, cross-reactive mAbs enhancing infectivity (n = 3) were found exclusively specific to Delta and Omicron variants. Notably, two mAbs that amplified in vitro the cytopathic effect of the Delta variant also exhibited neutralization against Omicron. These findings shed light on functional diversity of cross-reactive Abs generated during SARS-CoV-2 infection and illustrate how the balance between neutralizing and enhancing Abs facilitate variant emergence. |
| format | Article |
| id | doaj-art-725b95a4531942e5a2af76515eb2b678 |
| institution | OA Journals |
| issn | 2222-1751 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-725b95a4531942e5a2af76515eb2b6782025-08-20T02:20:36ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512024-12-0113110.1080/22221751.2024.2307510Neutralizing and enhancing monoclonal antibodies in SARS-CoV-2 convalescent patients: lessons from early variant infection and impact on shaping emerging variantsFrédéric Coutant0Franck Touret1Jean-Jacques Pin2Marina Alonzo3Cécile Baronti4Sandie Munier5Mikaël Attia6Xavier de Lamballerie7Tristan Ferry8Pierre Miossec9Immunogenomics and Inflammation Research Team, University of Lyon, Edouard Herriot Hospital, Lyon, FranceUnité des Virus Émergents (UVE: Aix-Marseille University - IRD 190 - Inserm 1207), Marseille, FranceEurobio Scientific/Dendritics – Edouard Herriot Hospital, Lyon, FranceImmunogenomics and Inflammation Research Team, University of Lyon, Edouard Herriot Hospital, Lyon, FranceUnité des Virus Émergents (UVE: Aix-Marseille University - IRD 190 - Inserm 1207), Marseille, FranceInstitut Pasteur, Université Paris Cité, CNRS UMR3569, Molecular Genetics of RNA Viruses Unit, Paris, FranceInstitut Pasteur, Université Paris Cité, CNRS UMR3569, Molecular Genetics of RNA Viruses Unit, Paris, FranceUnité des Virus Émergents (UVE: Aix-Marseille University - IRD 190 - Inserm 1207), Marseille, FranceDepartment of Infectious and Tropical Diseases, Hospices Civils of Lyon - Croix-Rousse Hospital, Lyon, FranceImmunogenomics and Inflammation Research Team, University of Lyon, Edouard Herriot Hospital, Lyon, FranceSerological studies of COVID-19 convalescent patients have identified polyclonal lineage-specific and cross-reactive antibodies (Abs), with varying effector functions against virus variants. Individual specificities of anti-SARS-CoV-2 Abs and their impact on infectivity by other variants have been little investigated to date. Here, we dissected at a monoclonal level neutralizing and enhancing Abs elicited by early variants and how they affect infectivity of emerging variants. B cells from 13 convalescent patients originally infected by D614G or Alpha variants were immortalized to isolate 445 naturally-produced anti-SARS-CoV-2 Abs. Monoclonal antibodies (mAbs) were tested for their abilities to impact the cytopathic effect of D614G, Delta, and Omicron (BA.1) variants. Ninety-eight exhibited robust neutralization against at least one of the three variant types, while 309 showed minimal or no impact on infectivity. Thirty-eight mAbs enhanced infectivity of SARS-CoV-2. Infection with D614G/Alpha variants generated variant-specific (65 neutralizing Abs, 35 enhancing Abs) and cross-reactive (18 neutralizing Abs, 3 enhancing Abs) mAbs. Interestingly, among the neutralizing mAbs with cross-reactivity restricted to two of the three variants tested, none demonstrated specific neutralization of the Delta and Omicron variants. In contrast, cross-reactive mAbs enhancing infectivity (n = 3) were found exclusively specific to Delta and Omicron variants. Notably, two mAbs that amplified in vitro the cytopathic effect of the Delta variant also exhibited neutralization against Omicron. These findings shed light on functional diversity of cross-reactive Abs generated during SARS-CoV-2 infection and illustrate how the balance between neutralizing and enhancing Abs facilitate variant emergence.https://www.tandfonline.com/doi/10.1080/22221751.2024.2307510COVID-19B cell repertoireantibody-dependent enhancementhuman monoclonal antibodyemerging variants |
| spellingShingle | Frédéric Coutant Franck Touret Jean-Jacques Pin Marina Alonzo Cécile Baronti Sandie Munier Mikaël Attia Xavier de Lamballerie Tristan Ferry Pierre Miossec Neutralizing and enhancing monoclonal antibodies in SARS-CoV-2 convalescent patients: lessons from early variant infection and impact on shaping emerging variants Emerging Microbes and Infections COVID-19 B cell repertoire antibody-dependent enhancement human monoclonal antibody emerging variants |
| title | Neutralizing and enhancing monoclonal antibodies in SARS-CoV-2 convalescent patients: lessons from early variant infection and impact on shaping emerging variants |
| title_full | Neutralizing and enhancing monoclonal antibodies in SARS-CoV-2 convalescent patients: lessons from early variant infection and impact on shaping emerging variants |
| title_fullStr | Neutralizing and enhancing monoclonal antibodies in SARS-CoV-2 convalescent patients: lessons from early variant infection and impact on shaping emerging variants |
| title_full_unstemmed | Neutralizing and enhancing monoclonal antibodies in SARS-CoV-2 convalescent patients: lessons from early variant infection and impact on shaping emerging variants |
| title_short | Neutralizing and enhancing monoclonal antibodies in SARS-CoV-2 convalescent patients: lessons from early variant infection and impact on shaping emerging variants |
| title_sort | neutralizing and enhancing monoclonal antibodies in sars cov 2 convalescent patients lessons from early variant infection and impact on shaping emerging variants |
| topic | COVID-19 B cell repertoire antibody-dependent enhancement human monoclonal antibody emerging variants |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2024.2307510 |
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