SARS-CoV-2 Omicron boosting induces de novo B cell response in humans
© 2023. The Author(s), under exclusive licence to Springer Nature Limited..
The primary two-dose SARS-CoV-2 mRNA vaccine series are strongly immunogenic in humans, but the emergence of highly infectious variants necessitated additional doses and the development of vaccines aimed at the new variants1-4. SARS-CoV-2 booster immunizations in humans primarily recruit pre-existing memory B cells5-9. However, it remains unclear whether the additional doses induce germinal centre reactions whereby re-engaged B cells can further mature, and whether variant-derived vaccines can elicit responses to variant-specific epitopes. Here we show that boosting with an mRNA vaccine against the original monovalent SARS-CoV-2 mRNA vaccine or the bivalent B.1.351 and B.1.617.2 (Beta/Delta) mRNA vaccine induced robust spike-specific germinal centre B cell responses in humans. The germinal centre response persisted for at least eight weeks, leading to significantly more mutated antigen-specific bone marrow plasma cell and memory B cell compartments. Spike-binding monoclonal antibodies derived from memory B cells isolated from individuals boosted with either the original SARS-CoV-2 spike protein, bivalent Beta/Delta vaccine or a monovalent Omicron BA.1-based vaccine predominantly recognized the original SARS-CoV-2 spike protein. Nonetheless, using a more targeted sorting approach, we isolated monoclonal antibodies that recognized the BA.1 spike protein but not the original SARS-CoV-2 spike protein from individuals who received the mRNA-1273.529 booster; these antibodies were less mutated and recognized novel epitopes within the spike protein, suggesting that they originated from naive B cells. Thus, SARS-CoV-2 booster immunizations in humans induce robust germinal centre B cell responses and can generate de novo B cell responses targeting variant-specific epitopes.
| Errataetall: | |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:617 |
|---|---|
| Enthalten in: |
Nature - 617(2023), 7961 vom: 13. Mai, Seite 592-598 |
| Sprache: |
Englisch |
|---|
| Links: |
|---|
| Themen: |
Antibodies, Monoclonal |
|---|
| Anmerkungen: |
Date Completed 23.05.2023 Date Revised 25.03.2024 published: Print-Electronic UpdateOf: bioRxiv. 2022 Sep 22;:. - PMID 36172127 Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41586-023-06025-4 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM35516454X |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM35516454X | ||
| 003 | DE-627 | ||
| 005 | 20240325234152.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41586-023-06025-4 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1346.xml |
| 035 | |a (DE-627)NLM35516454X | ||
| 035 | |a (NLM)37011668 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Alsoussi, Wafaa B |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a SARS-CoV-2 Omicron boosting induces de novo B cell response in humans |
| 264 | 1 | |c 2023 | |
| 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 23.05.2023 | ||
| 500 | |a Date Revised 25.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a UpdateOf: bioRxiv. 2022 Sep 22;:. - PMID 36172127 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s), under exclusive licence to Springer Nature Limited. | ||
| 520 | |a The primary two-dose SARS-CoV-2 mRNA vaccine series are strongly immunogenic in humans, but the emergence of highly infectious variants necessitated additional doses and the development of vaccines aimed at the new variants1-4. SARS-CoV-2 booster immunizations in humans primarily recruit pre-existing memory B cells5-9. However, it remains unclear whether the additional doses induce germinal centre reactions whereby re-engaged B cells can further mature, and whether variant-derived vaccines can elicit responses to variant-specific epitopes. Here we show that boosting with an mRNA vaccine against the original monovalent SARS-CoV-2 mRNA vaccine or the bivalent B.1.351 and B.1.617.2 (Beta/Delta) mRNA vaccine induced robust spike-specific germinal centre B cell responses in humans. The germinal centre response persisted for at least eight weeks, leading to significantly more mutated antigen-specific bone marrow plasma cell and memory B cell compartments. Spike-binding monoclonal antibodies derived from memory B cells isolated from individuals boosted with either the original SARS-CoV-2 spike protein, bivalent Beta/Delta vaccine or a monovalent Omicron BA.1-based vaccine predominantly recognized the original SARS-CoV-2 spike protein. Nonetheless, using a more targeted sorting approach, we isolated monoclonal antibodies that recognized the BA.1 spike protein but not the original SARS-CoV-2 spike protein from individuals who received the mRNA-1273.529 booster; these antibodies were less mutated and recognized novel epitopes within the spike protein, suggesting that they originated from naive B cells. Thus, SARS-CoV-2 booster immunizations in humans induce robust germinal centre B cell responses and can generate de novo B cell responses targeting variant-specific epitopes | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a Antibodies, Neutralizing |2 NLM | |
| 650 | 7 | |a Antibodies, Viral |2 NLM | |
| 650 | 7 | |a COVID-19 Vaccines |2 NLM | |
| 650 | 7 | |a Spike Glycoprotein, Coronavirus |2 NLM | |
| 650 | 7 | |a spike protein, SARS-CoV-2 |2 NLM | |
| 650 | 7 | |a Epitopes, B-Lymphocyte |2 NLM | |
| 700 | 1 | |a Malladi, Sameer Kumar |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Julian Q |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Zhuoming |e verfasserin |4 aut | |
| 700 | 1 | |a Ying, Baoling |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Wooseob |e verfasserin |4 aut | |
| 700 | 1 | |a Schmitz, Aaron J |e verfasserin |4 aut | |
| 700 | 1 | |a Lei, Tingting |e verfasserin |4 aut | |
| 700 | 1 | |a Horvath, Stephen C |e verfasserin |4 aut | |
| 700 | 1 | |a Sturtz, Alexandria J |e verfasserin |4 aut | |
| 700 | 1 | |a McIntire, Katherine M |e verfasserin |4 aut | |
| 700 | 1 | |a Evavold, Birk |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Fangjie |e verfasserin |4 aut | |
| 700 | 1 | |a Scheaffer, Suzanne M |e verfasserin |4 aut | |
| 700 | 1 | |a Fox, Isabella F |e verfasserin |4 aut | |
| 700 | 1 | |a Mirza, Senaa F |e verfasserin |4 aut | |
| 700 | 1 | |a Parra-Rodriguez, Luis |e verfasserin |4 aut | |
| 700 | 1 | |a Nachbagauer, Raffael |e verfasserin |4 aut | |
| 700 | 1 | |a Nestorova, Biliana |e verfasserin |4 aut | |
| 700 | 1 | |a Chalkias, Spyros |e verfasserin |4 aut | |
| 700 | 1 | |a Farnsworth, Christopher W |e verfasserin |4 aut | |
| 700 | 1 | |a Klebert, Michael K |e verfasserin |4 aut | |
| 700 | 1 | |a Pusic, Iskra |e verfasserin |4 aut | |
| 700 | 1 | |a Strnad, Benjamin S |e verfasserin |4 aut | |
| 700 | 1 | |a Middleton, William D |e verfasserin |4 aut | |
| 700 | 1 | |a Teefey, Sharlene A |e verfasserin |4 aut | |
| 700 | 1 | |a Whelan, Sean P J |e verfasserin |4 aut | |
| 700 | 1 | |a Diamond, Michael S |e verfasserin |4 aut | |
| 700 | 1 | |a Paris, Robert |e verfasserin |4 aut | |
| 700 | 1 | |a O'Halloran, Jane A |e verfasserin |4 aut | |
| 700 | 1 | |a Presti, Rachel M |e verfasserin |4 aut | |
| 700 | 1 | |a Turner, Jackson S |e verfasserin |4 aut | |
| 700 | 1 | |a Ellebedy, Ali H |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nature |d 1945 |g 617(2023), 7961 vom: 13. Mai, Seite 592-598 |w (DE-627)NLM000008257 |x 1476-4687 |7 nnns |
| 773 | 1 | 8 | |g volume:617 |g year:2023 |g number:7961 |g day:13 |g month:05 |g pages:592-598 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41586-023-06025-4 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 617 |j 2023 |e 7961 |b 13 |c 05 |h 592-598 | ||