Human type I IFN deficiency does not impair B cell response to SARS-CoV-2 mRNA vaccination

Author:

Sokal Aurélien1ORCID,Bastard Paul2345ORCID,Chappert Pascal16ORCID,Barba-Spaeth Giovanna7ORCID,Fourati Slim89ORCID,Vanderberghe Alexis610ORCID,Lagouge-Roussey Pauline610ORCID,Meyts Isabelle11ORCID,Gervais Adrian23ORCID,Bouvier-Alias Magali89ORCID,Azzaoui Imane610ORCID,Fernández Ignacio7ORCID,de la Selle Andréa1ORCID,Zhang Qian235ORCID,Bizien Lucy23ORCID,Pellier Isabelle1213ORCID,Linglart Agnès14ORCID,Rothenbuhler Anya14ORCID,Marcoux Estelle15ORCID,Anxionnat Raphael16ORCID,Cheikh Nathalie16ORCID,Léger Juliane17ORCID,Amador-Borrero Blanca18,Fouyssac Fanny19,Menut Vanessa20ORCID,Goffard Jean-Christophe21ORCID,Storey Caroline22ORCID,Demily Caroline23ORCID,Mallebranche Coralie1213ORCID,Troya Jesus24ORCID,Pujol Aurora25ORCID,Zins Marie26ORCID,Tiberghien Pierre2728ORCID,Gray Paul E.293031ORCID,McNaughton Peter3132ORCID,Sullivan Anna3132,Peake Jane313233ORCID,Levy Romain2334ORCID,Languille Laetitia10ORCID,Rodiguez-Gallego Carlos3536,Boisson Bertrand235ORCID,Gallien Sébastien37ORCID,Neven Bénédicte34ORCID,Michel Marc10,Godeau Bertrand10ORCID,Abel Laurent235ORCID,Rey Felix A.7ORCID,Weill Jean-Claude1ORCID,Reynaud Claude-Agnès1ORCID,Tangye Stuart G.313839ORCID,Casanova Jean-Laurent234540ORCID,Mahévas Matthieu1610ORCID

Affiliation:

1. Necker Enfants Malades Institute, INSERM U1151/CNRS UMR 8253, Action thématique incitative sur programme-Avenir Team Auto-Immune and Immune B cell, University Paris Cité, University Paris-Est-Créteil, Créteil, France 1

2. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France 2

3. Imagine Institute, University Paris Cité, Paris, France 3

4. Department of Pediatrics, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris, Paris, France 4

5. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 5

6. INSERM U955, team 2. Mondor Biomedical Research Institute, Paris-Est Créteil University, Créteil, France 6

7. Institut Pasteur, University Paris Cité, CNRS UMR 3569, Structural Virology Unit, Paris, France 7

8. Virology, Bacteriology, Hygiene and Mycology-Parasitology, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Créteil, France 8

9. INSERM U955, team 18. Mondor Biomedical Research Institute, Paris-Est Créteil University, Créteil, France 9

10. Departement of Internal Medicine, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Paris-Est Créteil University, Créteil, France 10

11. Department of Immunology and Microbiology, Laboratory for Inborn Errors of Immunity, Department of Pediatrics, University Hospitals Leuven and Katholieke Universiteit Leuven, Leuven, Belgium 11

12. Pediatric Immuno-hemato-oncology Unit, Centre Hospitalier Universitaire Angers, Angers, France 12

13. University Angers, Nantes university, Centre Hospitalier Universitaire Angers, INSERM, CRCI2NA, SFR ICAT, Angers, France 13

14. Departement of Pediatric Endocrinology, Bicêtre University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Saclay University, Le Kremlin-Bicêtre, France 14

15. Department of Pediatrics, Nord Franche Comté Hospital, Trévenans, France 15

16. Department of Pediatrics, Besançon Hospital, Besançon, France 16

17. Department of Pediatric Endocrinology and INSERM NeuroDiderot, Referral Centre for Endocrine, Growth and Development diseases, Assistance Publique-Hôpitaux de Paris Nord, University of Paris, Paris, France 17

18. Department of Internal Medicine, Lariboisière University Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris, Paris, France 18

19. Department of Pediatric Hemato-oncology, Childrens Hospital, Nancy University Hospital, Nancy, France 19

20. Department of Pediatrics, Mother-Child Hospital, Nantes, France 20

21. Department of Internal Medicine, Université Libre de Bruxelles—Hôpitaux Universitaire de Bruxelles, Erasme Hospital, Bruxelles, Belgique 21

22. Departement of Pediatric Endocrinology, Robert Debré Hospital, Assistance Publique Hôpitaux de Paris, Paris, France 22

23. GénoPsy Referral Center, Centre de Référence de Maladies Rares Rare Disease with Psychiatric Epression, Le Vinatier Hospital, Bron, France 23

24. Department of Internal Medicine, Infanta Leonor University Hospital, Madrid, Spain 24

25. Neurometabolic Diseases Laboratory, Institut d'Investigació Biomèdica de Bellvitge-Hospital Duran i Reynals, Centro de Investigación Biomédica en Red de Enfermededas Raras U759, and Catalan Institution of Research and Advanced Studies, Barcelona, Spain 25

26. University of Paris, University of Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines, INSERM UMS11, Villejuif, France 26

27. French Blood Agency, La Plaine Saint-Denis, France 27

28. UMR1098 RIGHT, INSERM, French Blood Agency, Franche-Comté University, Besançon, France 28

29. Department of Immunology and Infectious Diseases, Sydney Children’s Hospital, Randwick, New South Wales, Australia 29

30. School of Women’s and Children’s Health, University of New South Wales, Sydney, Australia 30

31. Clinical Immunogenomics Research Consortium of Australasia, Sydney, Australia 31

32. Queensland Paediatric Immunology and Allergy Service, Children's Health Queensland, Brisbane, Australia 32

33. University of Queensland, Brisbane, Australia 33

34. Department of Pediatric Immuno-Haematology and Rheumatology, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France 34

35. Department of Immunology, Hospital Universitario de G.C. Dr. Negrín, Canarian Health System, Las Palmas de Gran Canaria, Spain 35

36. University Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain 36

37. Department of Infectious Diseases, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Paris-Est Créteil University, Créteil, France 37

38. Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia 38

39. St Vincent’s Clinical School, Faculty of Medicine & Health, University of New South Wales, Sydney, New South Wales, Australia 39

40. Howard Hughes Medical Institute, New York, NY 40

Abstract

Inborn and acquired deficits of type I interferon (IFN) immunity predispose to life-threatening COVID-19 pneumonia. We longitudinally profiled the B cell response to mRNA vaccination in SARS-CoV-2 naive patients with inherited TLR7, IRF7, or IFNAR1 deficiency, as well as young patients with autoantibodies neutralizing type I IFNs due to autoimmune polyendocrine syndrome type-1 (APS-1) and older individuals with age-associated autoantibodies to type I IFNs. The receptor-binding domain spike protein (RBD)–specific memory B cell response in all patients was quantitatively and qualitatively similar to healthy donors. Sustained germinal center responses led to accumulation of somatic hypermutations in immunoglobulin heavy chain genes. The amplitude and duration of, and viral neutralization by, RBD-specific IgG serological response were also largely unaffected by TLR7, IRF7, or IFNAR1 deficiencies up to 7 mo after vaccination in all patients. These results suggest that induction of type I IFN is not required for efficient generation of a humoral response against SARS-CoV-2 by mRNA vaccines.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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