Omicron BA.1 breakthrough infection drives long-term remodeling of the memory B cell repertoire in vaccinated individuals
Summary How infection by a viral variant showing antigenic drift impacts a preformed mature human memory B cell (MBC) repertoire remains an open question. Here, we studied the MBC response up to 6 months after Omicron BA.1 breakthrough infection in individuals previously vaccinated with three doses of mRNA vaccine. Longitudinal analysis, using single-cell multi-omics and functional analysis of monoclonal antibodies from RBD-specific MBCs, revealed that a BA.1 breakthrough infection mostly recruited pre-existing cross-reactive MBCs with limitedde novoresponse against BA.1-restricted epitopes. Reorganization of clonal hierarchy and new rounds of germinal center reaction, however, combined to maintain diversity and induce progressive maturation of the MBC repertoire against common Hu-1 and BA.1, but not BA.5-restricted, SARS-CoV-2 Spike RBD epitopes. Such remodeling was further associated with marked improvement in overall neutralizing breadth and potency. These findings have fundamental implications for the design of future vaccination booster strategies..
| Medienart: |
|
|---|
Preprint| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 01. Feb. Zur Gesamtaufnahme - year:2023 |
|---|
| Sprache: |
Englisch |
|---|
| Links: |
Volltext [kostenfrei] |
|---|
| Themen: |
|---|
| doi: |
10.1101/2023.01.27.525575 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
XBI038535343 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | XBI038535343 | ||
| 003 | DE-627 | ||
| 005 | 20230429101654.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230130s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/2023.01.27.525575 |2 doi | |
| 035 | |a (DE-627)XBI038535343 | ||
| 035 | |a (biorXiv)10.1101/2023.01.27.525575 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Sokal, Aurélien |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Omicron BA.1 breakthrough infection drives long-term remodeling of the memory B cell repertoire in vaccinated individuals |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Summary How infection by a viral variant showing antigenic drift impacts a preformed mature human memory B cell (MBC) repertoire remains an open question. Here, we studied the MBC response up to 6 months after Omicron BA.1 breakthrough infection in individuals previously vaccinated with three doses of mRNA vaccine. Longitudinal analysis, using single-cell multi-omics and functional analysis of monoclonal antibodies from RBD-specific MBCs, revealed that a BA.1 breakthrough infection mostly recruited pre-existing cross-reactive MBCs with limitedde novoresponse against BA.1-restricted epitopes. Reorganization of clonal hierarchy and new rounds of germinal center reaction, however, combined to maintain diversity and induce progressive maturation of the MBC repertoire against common Hu-1 and BA.1, but not BA.5-restricted, SARS-CoV-2 Spike RBD epitopes. Such remodeling was further associated with marked improvement in overall neutralizing breadth and potency. These findings have fundamental implications for the design of future vaccination booster strategies. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
| 650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
| 700 | 1 | |a Barba-Spaeth, Giovanna |e verfasserin |4 aut | |
| 700 | 1 | |a Hunault, Lise |e verfasserin |4 aut | |
| 700 | 1 | |a Fernández, Ignacio |e verfasserin |4 aut | |
| 700 | 1 | |a Broketa, Matteo |e verfasserin |4 aut | |
| 700 | 1 | |a Meola, Annalisa |e verfasserin |4 aut | |
| 700 | 1 | |a Fourati, Slim |e verfasserin |4 aut | |
| 700 | 1 | |a Azzaoui, Imane |e verfasserin |4 aut | |
| 700 | 1 | |a Vandenberghe, Alexis |e verfasserin |4 aut | |
| 700 | 1 | |a Lagouge-Roussey, Pauline |e verfasserin |4 aut | |
| 700 | 1 | |a Broutin, Manon |e verfasserin |4 aut | |
| 700 | 1 | |a Roeser, Anais |e verfasserin |4 aut | |
| 700 | 1 | |a Bouvier-Alias, Magali |e verfasserin |4 aut | |
| 700 | 1 | |a Crickx, Etienne |e verfasserin |4 aut | |
| 700 | 1 | |a Languille, Laetitia |e verfasserin |4 aut | |
| 700 | 1 | |a Fournier, Morgane |e verfasserin |4 aut | |
| 700 | 1 | |a Michel, Marc |e verfasserin |4 aut | |
| 700 | 1 | |a Godeau, Bertrand |e verfasserin |4 aut | |
| 700 | 1 | |a Gallien, Sébastien |e verfasserin |4 aut | |
| 700 | 1 | |a Melica, Giovanna |e verfasserin |4 aut | |
| 700 | 1 | |a Nguyen, Yann |e verfasserin |4 aut | |
| 700 | 1 | |a Canoui-Poitrine, Florence |e verfasserin |4 aut | |
| 700 | 1 | |a Noizat-Pirenne, France |e verfasserin |4 aut | |
| 700 | 1 | |a Megret, Jérôme |e verfasserin |4 aut | |
| 700 | 1 | |a Pawlotsky, Jean-Michel |e verfasserin |4 aut | |
| 700 | 1 | |a Fillatreau, Simon |e verfasserin |4 aut | |
| 700 | 1 | |a Reynaud, Claude-Agnès |e verfasserin |4 aut | |
| 700 | 1 | |a Weill, Jean-Claude |e verfasserin |4 aut | |
| 700 | 1 | |a Rey, Félix A. |e verfasserin |4 aut | |
| 700 | 1 | |a Bruhns, Pierre |e verfasserin |4 aut | |
| 700 | 1 | |a Mahévas, Matthieu |e verfasserin |4 aut | |
| 700 | 1 | |a Chappert, Pascal |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t bioRxiv.org |g (2023) vom: 01. Feb. |
| 773 | 1 | 8 | |g year:2023 |g day:01 |g month:02 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/2023.01.27.525575 |z kostenfrei |3 Volltext |
| 912 | |a GBV_XBI | ||
| 912 | |a SSG-OLC-PHA | ||
| 951 | |a AR | ||
| 952 | |j 2023 |b 01 |c 02 | ||