SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines
Numerous safe and effective coronavirus disease 2019 vaccines have been developed worldwide that use various delivery technologies and engineering strategies. We show here that vaccines containing prefusion-stabilizing S mutations elicit antibody responses in humans with enhanced recognition of S and the S1 subunit relative to postfusion S as compared with vaccines lacking these mutations or natural infection. Prefusion S and S1 antibody binding titers positively and equivalently correlated with neutralizing activity, and depletion of S1-directed antibodies completely abrogated plasma neutralizing activity. We show that neutralizing activity is almost entirely directed to the S1 subunit and that variant cross-neutralization is mediated solely by receptor binding domain-specific antibodies. Our data provide a quantitative framework for guiding future S engineering efforts to develop vaccines with higher resilience to the emergence of variants than current technologies.
| Errataetall: | |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:7 |
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| Enthalten in: |
Science immunology - 7(2022), 78 vom: 23. Dez., Seite eadf1421 |
| Sprache: |
Englisch |
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| Links: |
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| Themen: |
Antibodies, Neutralizing |
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| Anmerkungen: |
Date Completed 27.12.2022 Date Revised 19.05.2023 published: Print-Electronic UpdateOf: bioRxiv. 2021 Dec 21;:. - PMID 34981060 Citation Status MEDLINE |
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| doi: |
10.1126/sciimmunol.adf1421 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM348696558 |
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| 245 | 1 | 0 | |a SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines |
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| 500 | |a Date Completed 27.12.2022 | ||
| 500 | |a Date Revised 19.05.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a UpdateOf: bioRxiv. 2021 Dec 21;:. - PMID 34981060 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Numerous safe and effective coronavirus disease 2019 vaccines have been developed worldwide that use various delivery technologies and engineering strategies. We show here that vaccines containing prefusion-stabilizing S mutations elicit antibody responses in humans with enhanced recognition of S and the S1 subunit relative to postfusion S as compared with vaccines lacking these mutations or natural infection. Prefusion S and S1 antibody binding titers positively and equivalently correlated with neutralizing activity, and depletion of S1-directed antibodies completely abrogated plasma neutralizing activity. We show that neutralizing activity is almost entirely directed to the S1 subunit and that variant cross-neutralization is mediated solely by receptor binding domain-specific antibodies. Our data provide a quantitative framework for guiding future S engineering efforts to develop vaccines with higher resilience to the emergence of variants than current technologies | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
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| 650 | 7 | |a Antibodies, Neutralizing |2 NLM | |
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| 700 | 1 | |a Park, Young-Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Stewart, Cameron |e verfasserin |4 aut | |
| 700 | 1 | |a Brown, Jack T |e verfasserin |4 aut | |
| 700 | 1 | |a Sharkey, William K |e verfasserin |4 aut | |
| 700 | 1 | |a Walls, Alexandra C |e verfasserin |4 aut | |
| 700 | 1 | |a Joshi, Anshu |e verfasserin |4 aut | |
| 700 | 1 | |a Sprouse, Kaitlin R |e verfasserin |4 aut | |
| 700 | 1 | |a McCallum, Matthew |e verfasserin |4 aut | |
| 700 | 1 | |a Tortorici, M Alejandra |e verfasserin |4 aut | |
| 700 | 1 | |a Franko, Nicholas M |e verfasserin |4 aut | |
| 700 | 1 | |a Logue, Jennifer K |e verfasserin |4 aut | |
| 700 | 1 | |a Mazzitelli, Ignacio G |e verfasserin |4 aut | |
| 700 | 1 | |a Nguyen, Annalee W |e verfasserin |4 aut | |
| 700 | 1 | |a Silva, Rui P |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Yimin |e verfasserin |4 aut | |
| 700 | 1 | |a Low, Jun Siong |e verfasserin |4 aut | |
| 700 | 1 | |a Jerak, Josipa |e verfasserin |4 aut | |
| 700 | 1 | |a Tiles, Sasha W |e verfasserin |4 aut | |
| 700 | 1 | |a Ahmed, Kumail |e verfasserin |4 aut | |
| 700 | 1 | |a Shariq, Asefa |e verfasserin |4 aut | |
| 700 | 1 | |a Dan, Jennifer M |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Zeli |e verfasserin |4 aut | |
| 700 | 1 | |a Weiskopf, Daniela |e verfasserin |4 aut | |
| 700 | 1 | |a Sette, Alessandro |e verfasserin |4 aut | |
| 700 | 1 | |a Snell, Gyorgy |e verfasserin |4 aut | |
| 700 | 1 | |a Posavad, Christine M |e verfasserin |4 aut | |
| 700 | 1 | |a Iqbal, Najeeha Talat |e verfasserin |4 aut | |
| 700 | 1 | |a Geffner, Jorge |e verfasserin |4 aut | |
| 700 | 1 | |a Bandera, Alessandra |e verfasserin |4 aut | |
| 700 | 1 | |a Gori, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Sallusto, Federica |e verfasserin |4 aut | |
| 700 | 1 | |a Maynard, Jennifer A |e verfasserin |4 aut | |
| 700 | 1 | |a Crotty, Shane |e verfasserin |4 aut | |
| 700 | 1 | |a Van Voorhis, Wesley C |e verfasserin |4 aut | |
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| 700 | 1 | |a Grifantini, Renata |e verfasserin |4 aut | |
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| 700 | 1 | |a Corti, Davide |e verfasserin |4 aut | |
| 700 | 1 | |a Veesler, David |e verfasserin |4 aut | |
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