Evidence of antigenic drift in the fusion machinery core of SARS-CoV-2 spike
Antigenic drift of SARS-CoV-2 is typically defined by mutations in the N-terminal domain and receptor binding domain of spike protein. In contrast, whether antigenic drift occurs in the S2 domain remains largely elusive. Here, we perform a deep mutational scanning experiment to identify S2 mutations that affect binding of SARS-CoV-2 spike to three S2 apex public antibodies. Our results indicate that spatially diverse mutations, including D950N and Q954H, which are observed in Delta and Omicron variants, respectively, weaken the binding of spike to these antibodies. Although S2 apex antibodies are known to be nonneutralizing, we show that they confer protection in vivo through Fc-mediated effector functions. Overall, this study indicates that the S2 domain of SARS-CoV-2 spike can undergo antigenic drift, which represents a potential challenge for the development of more universal coronavirus vaccines.
| 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), 15 vom: 09. Apr., Seite e2317222121 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Tan, Timothy J C [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Antibodies |
|---|
| Anmerkungen: |
Date Completed 03.04.2024 Date Revised 14.04.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1073/pnas.2317222121 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM370466799 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM370466799 | ||
| 003 | DE-627 | ||
| 005 | 20240415232314.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240403s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1073/pnas.2317222121 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1375.xml |
| 035 | |a (DE-627)NLM370466799 | ||
| 035 | |a (NLM)38557175 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Tan, Timothy J C |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Evidence of antigenic drift in the fusion machinery core of SARS-CoV-2 spike |
| 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 03.04.2024 | ||
| 500 | |a Date Revised 14.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Antigenic drift of SARS-CoV-2 is typically defined by mutations in the N-terminal domain and receptor binding domain of spike protein. In contrast, whether antigenic drift occurs in the S2 domain remains largely elusive. Here, we perform a deep mutational scanning experiment to identify S2 mutations that affect binding of SARS-CoV-2 spike to three S2 apex public antibodies. Our results indicate that spatially diverse mutations, including D950N and Q954H, which are observed in Delta and Omicron variants, respectively, weaken the binding of spike to these antibodies. Although S2 apex antibodies are known to be nonneutralizing, we show that they confer protection in vivo through Fc-mediated effector functions. Overall, this study indicates that the S2 domain of SARS-CoV-2 spike can undergo antigenic drift, which represents a potential challenge for the development of more universal coronavirus vaccines | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a S2 domain | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a antibody | |
| 650 | 4 | |a deep mutational scanning | |
| 650 | 4 | |a spike | |
| 650 | 7 | |a Antibodies |2 NLM | |
| 650 | 7 | |a Spike Glycoprotein, Coronavirus |2 NLM | |
| 650 | 7 | |a Antibodies, Viral |2 NLM | |
| 650 | 7 | |a spike protein, SARS-CoV-2 |2 NLM | |
| 700 | 1 | |a Verma, Abhishek K |e verfasserin |4 aut | |
| 700 | 1 | |a Odle, Abby |e verfasserin |4 aut | |
| 700 | 1 | |a Lei, Ruipeng |e verfasserin |4 aut | |
| 700 | 1 | |a Meyerholz, David K |e verfasserin |4 aut | |
| 700 | 1 | |a Matreyek, Kenneth A |e verfasserin |4 aut | |
| 700 | 1 | |a Perlman, Stanley |e verfasserin |4 aut | |
| 700 | 1 | |a Wong, Lok-Yin Roy |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Nicholas C |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), 15 vom: 09. Apr., Seite e2317222121 |w (DE-627)NLM000008982 |x 1091-6490 |7 nnns |
| 773 | 1 | 8 | |g volume:121 |g year:2024 |g number:15 |g day:09 |g month:04 |g pages:e2317222121 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1073/pnas.2317222121 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 121 |j 2024 |e 15 |b 09 |c 04 |h e2317222121 | ||