SARS-CoV-2 Omicron BA.1 breakthrough infection drives late remodeling of the memory B cell repertoire in vaccinated individuals

被引：6

作者：

Sokal, Aurelien ^{[1
,2
,3
]}

Barba-Spaeth, Giovanna ^{[4
]}

Hunault, Lise ^{[5
,6
,7
]}

Fernandez, Ignacio ^{[4
]}

Broketa, Matteo ^{[5
,6
]}

Meola, Annalisa ^{[4
]}

Fourati, Slim ^{[8
,9
]}

Azzaoui, Imane ^{[3
,10
]}

Vandenberghe, Alexis ^{[1
,3
,10
]}

Lagouge-Roussey, Pauline ^{[1
,3
,10
]}

Broutin, Manon ^{[1
,10
]}

Roeser, Anais ^{[1
,3
]}

Bouvier-Alias, Magali ^{[8
,9
]}

Crickx, Etienne ^{[1
,3
,10
]}

Languille, Laetitia ^{[3
]}

Fournier, Morgane ^{[1
,3
]}

Michel, Marc ^{[3
]}

Godeau, Bertrand ^{[3
]}

Gallien, Sebastien ^{[11
]}

Melica, Giovanna ^{[11
]}

Nguyen, Yann ^{[12
]}

Canoui-Poitrine, Florence ^{[13
]}

Pirenne, France ^{[9
,14
]}

Megret, Jerome ^{[15
]}

Pawlotsky, Jean-Michel ^{[8
,9
]}

Fillatreau, Simon ^{[16
]}

Reynaud, Claude-Agnes ^{[1
]}

Weill, Jean-Claude ^{[1
]}

Rey, Felix A. ^{[4
]}

Bruhns, Pierre ^{[5
]}

Mahevas, Matthieu ^{[1
,3
,10
]}

Chappert, Pascal ^{[1
,10
]}

机构：

[1] Univ Paris Est Creteil, Univ Paris Cite, Inst Necker Enfants Malad, Act Themat Incitat Programme,INSERM,U1151,CNRS,UMR, Creteil, France

[2] Univ Paris Cite, Hop Beaujon, AP HP, Serv Med Interne, Clichy, France

[3] Univ Paris Est Creteil UPEC, AP HP, Ctr Hosp Univ Henri Mondor, Serv Med Interne, Creteil, France

[4] Univ Paris Cite, Inst Pasteur, Unite Virol Struct, CNRS,UMR 3569, Paris, France

[5] Univ Paris Cite, Inst Pasteur, Unit Antibodies Therapy & Pathol, INSERM,UMR1222, Paris, France

[6] Sorbonne Univ, ED394, Paris, France

[7] Sorbonne Univ, CNRS, Ctr Immunol & Malad Infectieuses CIMI Paris, INSERM, F-75013 Paris, France

[8] CHU Henri Mondor, AP HP, Dept Virol Bacteriol Hyg & Mycol Parasitol, Creteil, France

[9] Univ Paris Est Creteil UPEC, Inst Mondor Rech Biomed IMRB, INSERM, U955, Equipe 18, Creteil, France

[10] Univ Paris Est Creteil UPEC, Inst Mondor Rech Biomed IMRB, INSERM, U955, Equipe 2, Creteil, France

[11] Univ Paris Est Creteil UPEC, CHU Henri Mondor, AP HP, Serv Malad Infectieuses, Creteil, France

[12] CHU Cochin, AP HP, Serv Med Interne, Paris, France

[13] Univ Paris Est Creteil UPEC, CHU Henri Mondor, Inst Mondor Rech Biomed IMRB, AP HP,Dept Sante Publ,Unite Rech Clin URC,CEpiA Cl, Creteil, France

[14] Etab Francais Sang EFS Ile France, Creteil, France

[15] CNRS, Plateforme Cytometrie Flux, Struct Federat Rech Necker, INSERM,US24,UMS3633, Paris, France

[16] Univ Paris, Inst Necker Enfants Malad INEM, INSERM, CNRS,UMR 8253,U1151, Paris, France

来源：

IMMUNITY | 2023年 / 56卷 / 09期

关键词：

MATURATION; ANTIBODIES; RESPONSES;

D O I：

10.1016/j.immuni.2023.07.007

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 SARS-CoV-2 Omicron BA.1 breakthrough infection in individuals previously vaccinated with three doses of the COVID-19 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 re-cruited pre-existing cross-reactive MBCs with limited de novo response against BA.1-restricted epitopes. Reorganization of clonal hierarchy and new rounds of germinal center reactions, however, combined to main-tain 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 a marked improvement in overall neutralizing breadth and potency. These findings have fundamental implica-tions for the design of future vaccination booster strategies.

引用

页码：2137 / +

页数：23

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