High-resolution map of the Fc-functions mediated by COVID-19 neutralizing antibodies
ABSTRACT A growing body of evidence shows that Fc-dependent antibody effector functions play an important role in protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To unravel the mechanisms that drive these responses, we analyzed the phagocytosis and complement deposition mediated by a panel of 482 human monoclonal antibodies (nAbs) neutralizing the original Wuhan virus, expressed as recombinant IgG1. Our study confirmed that nAbs no longer neutralizing SARS-CoV-2 Omicron variants can retain their Fc-functions. Surprisingly, we found that nAbs with the most potent Fc-function recognize the N- terminal domain, followed by those targeting Class 3 epitopes in the receptor binding domain. Interestingly, nAbs direct against the Class 1/2 epitopes in the receptor binding motif, which are the most potent in neutralizing the virus, were the weakest in Fc-functions. The divergent properties of the neutralizing and Fc- function mediating antibodies were confirmed by the use of different B cell germlines and by the observation that Fc-functions of polyclonal sera differ from the profile observed with nAbs, suggesting that not-neutralizing antibodies also contribute to Fc-functions. These data provide a high-resolution picture of the Fc-antibody response to SARS-CoV-2 and suggest that the Fc contribution should be considered for the design of improved vaccines, the selection of therapeutic antibodies and the evaluation of correlates of protection..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 29. Apr. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Paciello, Ida [VerfasserIn] |
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| doi: |
10.1101/2023.07.10.548360 |
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| PPN (Katalog-ID): |
XBI040181979 |
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| 520 | |a ABSTRACT A growing body of evidence shows that Fc-dependent antibody effector functions play an important role in protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To unravel the mechanisms that drive these responses, we analyzed the phagocytosis and complement deposition mediated by a panel of 482 human monoclonal antibodies (nAbs) neutralizing the original Wuhan virus, expressed as recombinant IgG1. Our study confirmed that nAbs no longer neutralizing SARS-CoV-2 Omicron variants can retain their Fc-functions. Surprisingly, we found that nAbs with the most potent Fc-function recognize the N- terminal domain, followed by those targeting Class 3 epitopes in the receptor binding domain. Interestingly, nAbs direct against the Class 1/2 epitopes in the receptor binding motif, which are the most potent in neutralizing the virus, were the weakest in Fc-functions. The divergent properties of the neutralizing and Fc- function mediating antibodies were confirmed by the use of different B cell germlines and by the observation that Fc-functions of polyclonal sera differ from the profile observed with nAbs, suggesting that not-neutralizing antibodies also contribute to Fc-functions. These data provide a high-resolution picture of the Fc-antibody response to SARS-CoV-2 and suggest that the Fc contribution should be considered for the design of improved vaccines, the selection of therapeutic antibodies and the evaluation of correlates of protection. | ||
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