High-resolution map of the Fc functions mediated by COVID-19-neutralizing antibodies
A growing body of evidence shows that fragment crystallizable (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 non-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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:121 |
|---|---|
| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 121(2024), 3 vom: 16. Jan., Seite e2314730121 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Paciello, Ida [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Antibodies |
|---|
| Anmerkungen: |
Date Completed 12.01.2024 Date Revised 24.01.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1073/pnas.2314730121 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM366891154 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM366891154 | ||
| 003 | DE-627 | ||
| 005 | 20240124232046.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240114s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1073/pnas.2314730121 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1269.xml |
| 035 | |a (DE-627)NLM366891154 | ||
| 035 | |a (NLM)38198525 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Paciello, Ida |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a High-resolution map of the Fc functions mediated by COVID-19-neutralizing antibodies |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 12.01.2024 | ||
| 500 | |a Date Revised 24.01.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a A growing body of evidence shows that fragment crystallizable (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 non-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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a B cell germlines | |
| 650 | 4 | |a Fc function | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a antibodies | |
| 650 | 7 | |a Antibodies, Neutralizing |2 NLM | |
| 650 | 7 | |a Epitopes |2 NLM | |
| 700 | 1 | |a Maccari, Giuseppe |e verfasserin |4 aut | |
| 700 | 1 | |a Pantano, Elisa |e verfasserin |4 aut | |
| 700 | 1 | |a Andreano, Emanuele |e verfasserin |4 aut | |
| 700 | 1 | |a Rappuoli, Rino |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Proceedings of the National Academy of Sciences of the United States of America |d 1915 |g 121(2024), 3 vom: 16. Jan., Seite e2314730121 |w (DE-627)NLM000008982 |x 1091-6490 |7 nnns |
| 773 | 1 | 8 | |g volume:121 |g year:2024 |g number:3 |g day:16 |g month:01 |g pages:e2314730121 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1073/pnas.2314730121 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 121 |j 2024 |e 3 |b 16 |c 01 |h e2314730121 | ||