SARS-CoV-2 Omicron BA.1 breakthrough infection drives late remodeling of the memory B cell repertoire in vaccinated individuals
Aurélien Sokal
(1, 2, 3, 4)
,
Giovanna Barba-Spaeth
(5)
,
Lise Hunault
(6, 7, 8)
,
Ignacio Fernandez
(5)
,
Matteo Broketa
(6, 7)
,
Annalisa Meola
(5)
,
Slim Fourati
(4, 9)
,
Imane Azzaoui
(4, 10)
,
Alexis Vandenberghe
(1, 4, 10)
,
Pauline Lagouge-Roussey
(1, 4, 10)
,
Manon Broutin
(1, 10)
,
Anais Roeser
(1, 4)
,
Magali Bouvier-Alias
(4, 9)
,
Etienne Crickx
(1, 4, 10)
,
Laetitia Languille
(4)
,
Morgane Fournier
(1, 4)
,
Marc Michel
(4)
,
Bertrand Godeau
(4)
,
Sébastien Gallien
(4)
,
Giovanna Melica
(4)
,
Yann Nguyen
(11)
,
Florence Canoui-Poitrine
(12)
,
France Pirenne
(9, 13)
,
Jérôme Megret
(14, 15)
,
Jean-Michel Pawlotsky
(4, 9)
,
Simon Fillatreau
(1)
,
Claude-Agnès Reynaud
(1)
,
Jean-Claude Weill
(1)
,
Félix Rey
(5)
,
Pierre Bruhns
(6)
,
Matthieu Mahévas
(1, 4, 10)
,
Pascal Chappert
(1, 10)
1
INEM - UM 111 (UMR 8253 / U1151) -
Institut Necker Enfants-Malades
2 Hôpital Beaujon [AP-HP]
3 UPCité - Université Paris Cité
4 Hôpital Henri Mondor
5 Virologie Structurale - Structural Virology
6 Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology
7 ED 394 - Physiologie, physiopathologie et thérapeutique
8 CIMI - Centre d'Immunologie et des Maladies Infectieuses
9 Inserm U955 - Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18)
10 U955 Inserm - UPEC - IMRB - "Transfusion et Maladies du Globule Rouge" [Créteil]
11 Hôpital Cochin [AP-HP]
12 U955 Inserm - UPEC - IMRB - CEPIA/"Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health" [Créteil]
13 EFS - Etablissement Français du Sang
14 UAR 3633 / US24 - Structure Fédérative de Recherche Necker
15 CYBIO - Plateforme Cytométrie et Immunobiologie [Institut Cochin]
2 Hôpital Beaujon [AP-HP]
3 UPCité - Université Paris Cité
4 Hôpital Henri Mondor
5 Virologie Structurale - Structural Virology
6 Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology
7 ED 394 - Physiologie, physiopathologie et thérapeutique
8 CIMI - Centre d'Immunologie et des Maladies Infectieuses
9 Inserm U955 - Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18)
10 U955 Inserm - UPEC - IMRB - "Transfusion et Maladies du Globule Rouge" [Créteil]
11 Hôpital Cochin [AP-HP]
12 U955 Inserm - UPEC - IMRB - CEPIA/"Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health" [Créteil]
13 EFS - Etablissement Français du Sang
14 UAR 3633 / US24 - Structure Fédérative de Recherche Necker
15 CYBIO - Plateforme Cytométrie et Immunobiologie [Institut Cochin]
Giovanna Barba-Spaeth
- Fonction : Auteur
- PersonId : 735128
- IdHAL : giovanna-barba-spaeth
- ORCID : 0000-0003-2069-9501
Ignacio Fernandez
- Fonction : Auteur
- PersonId : 1212646
- IdHAL : ignacio-fernandez
Annalisa Meola
- Fonction : Auteur
- PersonId : 754880
- IdHAL : annalisa-meola
- ORCID : 0000-0003-2582-4463
Sébastien Gallien
- Fonction : Auteur
- PersonId : 760825
- IdHAL : sebastien-gallien
- ORCID : 0000-0002-8033-0936
Simon Fillatreau
- Fonction : Auteur
- PersonId : 1235806
- ORCID : 0000-0002-7730-9917
- IdRef : 076345475
Pierre Bruhns
- Fonction : Auteur
- PersonId : 183222
- IdHAL : pierre-bruhns
- ORCID : 0000-0002-4709-8936
- IdRef : 168916401
Pascal Chappert
- Fonction : Auteur correspondant
Résumé
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 recruited 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 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 a marked improvement in overall neutralizing breadth and potency. These findings have fundamental implications for the design of future vaccination booster strategies.