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

Aurélien Sokal (1) , Paul Bastard (2, 3) , Pascal Chappert (1, 4) , Giovanna Barba-Spaeth (5) , Slim Fourati (6, 4) , Alexis Vanderberghe (6, 4) , Pauline Lagouge-Roussey (6, 4) , Isabelle Meyts (7) , Adrian Gervais (2) , Magali Bouvier-Alias , Imane Azzaoui , Ignacio Fernández (5) , Andréa de la Selle , Qian Zhang , Lucy Bizien , Isabelle Pellier (8, 9) , Agnès Linglart (10, 11) , Anya Rothenbuhler , Estelle Marcoux (12) , Raphael Anxionnat (13) , Nathalie Cheikh (13) , Juliane Léger (14) , Blanca Amador-Borrero (15) , Fanny Fouyssac (16) , Vanessa Menut (17) , Jean-Christophe Goffard (18) , Caroline Storey (19) , Caroline Demily (20) , Coralie Mallebranche , Jesus Troya (21) , Aurora Pujol (22) , Marie Zins (23, 11, 24) , Pierre Tiberghien (25) , Paul Gray (26, 27) , Peter Mcnaughton (28) , Anna Sullivan (28) , Jane Peake (28) , Romain Levy (2, 29) , Laetitia Languille , Carlos Rodiguez-Gallego (30) , Bertrand Boisson , Sébastien Gallien , Bénédicte Neven , Marc Michel , Bertrand Godeau , Laurent Abel , Felix Rey (5) , Jean-Claude Weill , Claude-Agnès Reynaud , Stuart Tangye (31, 27) , Jean-Laurent Casanova (2, 29, 3, 32) , Matthieu Mahévas (1, 4)

1 INEM - UM 111 (UMR 8253 / U1151) - Institut Necker Enfants-Malades
2 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
3 Rockefeller University [New York]
4 IMRB - Institut Mondor de Recherche Biomédicale
5 Virologie Structurale - Structural Virology
6 CHU Henri Mondor
7 KU Leuven - Catholic University of Leuven - Katholieke Universiteit Leuven
8 CHU Angers - Centre Hospitalier Universitaire d'Angers
9 UA - Université d'Angers
10 AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)
11 Université Paris-Saclay
12 HNFC - Hôpital Nord Franche-Comté [Hôpital de Trévenans]
13 Service de pédiatrie [CHRU Besançon]
14 AP-HP. Nord - Université Paris Cité
15 Hôpital Lariboisière-Fernand-Widal [APHP]
16 CHU Nancy - Centre Hospitalier Universitaire de Nancy
17 Hôpital Mère-Enfant [Hôpital Hôtel Dieu, Nantes]
18 ULB - Université libre de Bruxelles
19 Hôpital Robert Debré
20 Centre Hospitalier le Vinatier [Bron]
21 Hospital Universitario Infanta Leonor [Madrid]
22 IDIBELL - Institut d'Investigació Biomèdica de Bellvitge [Barcelone]
23 UPCité - Université Paris Cité
24 UVSQ - Université de Versailles Saint-Quentin-en-Yvelines
25 EFS - Etablissement Français du Sang [La Plaine Saint-Denis]
26 Sydney Children's hospital
27 UNSW - University of New South Wales [Sydney]
28 CHQ - Children’s Health Queensland [Brisbane]
29 CHU Necker - Enfants Malades [AP-HP]
30 Universidad Fernando Pessoa Canarias [Las Palmas de Gran Canaria, Spain]
31 Garvan Institute of medical research
32 HHMI - Howard Hughes Medical Institute [New York]

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.

Domains: Life Sciences [q-bio]; Immunology; Life Sciences [q-bio]; Immunology; Vaccinology

Aurélien Sokal, Paul Bastard, Pascal Chappert, Giovanna Barba-Spaeth, Slim Fourati, et al.. Human type I IFN deficiency does not impair B cell response to SARS-CoV-2 mRNA vaccination. Journal of Experimental Medicine, 2023, 220 (1), pp.e20220258. ⟨10.1084/jem.20220258⟩. ⟨pasteur-03847416⟩