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

doi:10.1084/jem.20220258

. 2023 Jan 2;220(1):e20220258.

doi: 10.1084/jem.20220258. Epub 2022 Nov 7.

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

Aurélien Sokal^#¹, Paul Bastard^#^{2

3

4

5}, Pascal Chappert^#^{1

6}, Giovanna Barba-Spaeth^#⁷, Slim Fourati^{8

9}, Alexis Vanderberghe^{6

10}, Pauline Lagouge-Roussey^{6

10}, Isabelle Meyts¹¹, Adrian Gervais^{2

3}, Magali Bouvier-Alias^{8

9}, Imane Azzaoui^{6

10}, Ignacio Fernández⁷, Andréa de la Selle¹, Qian Zhang^{2

3

5}, Lucy Bizien^{2

3}, Isabelle Pellier^{12

13}, Agnès Linglart¹⁴, Anya Rothenbuhler¹⁴, Estelle Marcoux¹⁵, Raphael Anxionnat¹⁶, Nathalie Cheikh¹⁶, Juliane Léger¹⁷, Blanca Amador-Borrero¹⁸, Fanny Fouyssac¹⁹, Vanessa Menut²⁰, Jean-Christophe Goffard²¹, Caroline Storey²², Caroline Demily²³, Coralie Mallebranche^{12

13}, Jesus Troya²⁴, Aurora Pujol²⁵, Marie Zins²⁶, Pierre Tiberghien^{27

28}, Paul E Gray^{29

30

31}, Peter McNaughton^{31

32}, Anna Sullivan^{31

32}, Jane Peake^{31

32

33}, Romain Levy^{2

3

34}, Laetitia Languille¹⁰, Carlos Rodiguez-Gallego^{35

36}, Bertrand Boisson^{2

3

5}, Sébastien Gallien³⁷, Bénédicte Neven³⁴, Marc Michel¹⁰, Bertrand Godeau¹⁰, Laurent Abel^{2

3

5}, Felix A Rey⁷, Jean-Claude Weill¹, Claude-Agnès Reynaud¹, Stuart G Tangye^{31

38

39}, Jean-Laurent Casanova^{2

3

4

5

40}, Matthieu Mahévas^{1

6

10}

Affiliations

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.
² Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.
³ Imagine Institute, University Paris Cité, Paris, France.
⁴ Department of Pediatrics, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris, Paris, France.
⁵ St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.
⁶ INSERM U955, team 2. Mondor Biomedical Research Institute, Paris-Est Créteil University, Créteil, France.
⁷ Institut Pasteur, University Paris Cité, CNRS UMR 3569, Structural Virology Unit, Paris, France.
⁸ Virology, Bacteriology, Hygiene and Mycology-Parasitology, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Créteil, France.
⁹ INSERM U955, team 18. Mondor Biomedical Research Institute, Paris-Est Créteil University, Créteil, France.
¹⁰ Departement of Internal Medicine, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Paris-Est Créteil University, Créteil, France.
¹¹ Department of Immunology and Microbiology, Laboratory for Inborn Errors of Immunity, Department of Pediatrics, University Hospitals Leuven and Katholieke Universiteit Leuven, Leuven, Belgium.
¹² Pediatric Immuno-hemato-oncology Unit, Centre Hospitalier Universitaire Angers, Angers, France.
¹³ University Angers, Nantes university, Centre Hospitalier Universitaire Angers, INSERM, CRCI2NA, SFR ICAT, Angers, France.
¹⁴ Departement of Pediatric Endocrinology, Bicêtre University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Saclay University, Le Kremlin-Bicêtre, France.
¹⁵ Department of Pediatrics, Nord Franche Comté Hospital, Trévenans, France.
¹⁶ Department of Pediatrics, Besançon Hospital, Besançon, France.
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.
¹⁸ Department of Internal Medicine, Lariboisière University Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris, Paris, France.
¹⁹ Department of Pediatric Hemato-oncology, Childrens Hospital, Nancy University Hospital, Nancy, France.
²⁰ Department of Pediatrics, Mother-Child Hospital, Nantes, France.
²¹ Department of Internal Medicine, Université Libre de Bruxelles-Hôpitaux Universitaire de Bruxelles, Erasme Hospital, Bruxelles, Belgique.
²² Departement of Pediatric Endocrinology, Robert Debré Hospital, Assistance Publique Hôpitaux de Paris, Paris, France.
²³ GénoPsy Referral Center, Centre de Référence de Maladies Rares Rare Disease with Psychiatric Epression, Le Vinatier Hospital, Bron, France.
²⁴ Department of Internal Medicine, Infanta Leonor University Hospital, Madrid, Spain.
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.
²⁶ University of Paris, University of Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines, INSERM UMS11, Villejuif, France.
²⁷ French Blood Agency, La Plaine Saint-Denis, France.
²⁸ UMR1098 RIGHT, INSERM, French Blood Agency, Franche-Comté University, Besançon, France.
²⁹ Department of Immunology and Infectious Diseases, Sydney Children's Hospital, Randwick, New South Wales, Australia.
³⁰ School of Women's and Children's Health, University of New South Wales, Sydney, Australia.
³¹ Clinical Immunogenomics Research Consortium of Australasia, Sydney, Australia.
³² Queensland Paediatric Immunology and Allergy Service, Children's Health Queensland, Brisbane, Australia.
³³ University of Queensland, Brisbane, Australia.
³⁴ Department of Pediatric Immuno-Haematology and Rheumatology, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
³⁵ Department of Immunology, Hospital Universitario de G.C. Dr. Negrín, Canarian Health System, Las Palmas de Gran Canaria, Spain.
³⁶ University Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain.
³⁷ Department of Infectious Diseases, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Paris-Est Créteil University, Créteil, France.
³⁸ Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
³⁹ St Vincent's Clinical School, Faculty of Medicine & Health, University of New South Wales, Sydney, New South Wales, Australia.
⁴⁰ Howard Hughes Medical Institute, New York, NY.

^# Contributed equally.

PMID: 36342455
PMCID: PMC9814155
DOI: 10.1084/jem.20220258

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

Aurélien Sokal et al. J Exp Med. 2023.

. 2023 Jan 2;220(1):e20220258.

doi: 10.1084/jem.20220258. Epub 2022 Nov 7.

Authors

Affiliations

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.
² Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.
³ Imagine Institute, University Paris Cité, Paris, France.
⁴ Department of Pediatrics, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris, Paris, France.
⁵ St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.
⁶ INSERM U955, team 2. Mondor Biomedical Research Institute, Paris-Est Créteil University, Créteil, France.
⁷ Institut Pasteur, University Paris Cité, CNRS UMR 3569, Structural Virology Unit, Paris, France.
⁸ Virology, Bacteriology, Hygiene and Mycology-Parasitology, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Créteil, France.
⁹ INSERM U955, team 18. Mondor Biomedical Research Institute, Paris-Est Créteil University, Créteil, France.
¹⁰ Departement of Internal Medicine, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Paris-Est Créteil University, Créteil, France.
¹¹ Department of Immunology and Microbiology, Laboratory for Inborn Errors of Immunity, Department of Pediatrics, University Hospitals Leuven and Katholieke Universiteit Leuven, Leuven, Belgium.
¹² Pediatric Immuno-hemato-oncology Unit, Centre Hospitalier Universitaire Angers, Angers, France.
¹³ University Angers, Nantes university, Centre Hospitalier Universitaire Angers, INSERM, CRCI2NA, SFR ICAT, Angers, France.
¹⁴ Departement of Pediatric Endocrinology, Bicêtre University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Saclay University, Le Kremlin-Bicêtre, France.
¹⁵ Department of Pediatrics, Nord Franche Comté Hospital, Trévenans, France.
¹⁶ Department of Pediatrics, Besançon Hospital, Besançon, France.
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.
¹⁸ Department of Internal Medicine, Lariboisière University Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris, Paris, France.
¹⁹ Department of Pediatric Hemato-oncology, Childrens Hospital, Nancy University Hospital, Nancy, France.
²⁰ Department of Pediatrics, Mother-Child Hospital, Nantes, France.
²¹ Department of Internal Medicine, Université Libre de Bruxelles-Hôpitaux Universitaire de Bruxelles, Erasme Hospital, Bruxelles, Belgique.
²² Departement of Pediatric Endocrinology, Robert Debré Hospital, Assistance Publique Hôpitaux de Paris, Paris, France.
²³ GénoPsy Referral Center, Centre de Référence de Maladies Rares Rare Disease with Psychiatric Epression, Le Vinatier Hospital, Bron, France.
²⁴ Department of Internal Medicine, Infanta Leonor University Hospital, Madrid, Spain.
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.
²⁶ University of Paris, University of Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines, INSERM UMS11, Villejuif, France.
²⁷ French Blood Agency, La Plaine Saint-Denis, France.
²⁸ UMR1098 RIGHT, INSERM, French Blood Agency, Franche-Comté University, Besançon, France.
²⁹ Department of Immunology and Infectious Diseases, Sydney Children's Hospital, Randwick, New South Wales, Australia.
³⁰ School of Women's and Children's Health, University of New South Wales, Sydney, Australia.
³¹ Clinical Immunogenomics Research Consortium of Australasia, Sydney, Australia.
³² Queensland Paediatric Immunology and Allergy Service, Children's Health Queensland, Brisbane, Australia.
³³ University of Queensland, Brisbane, Australia.
³⁴ Department of Pediatric Immuno-Haematology and Rheumatology, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
³⁵ Department of Immunology, Hospital Universitario de G.C. Dr. Negrín, Canarian Health System, Las Palmas de Gran Canaria, Spain.
³⁶ University Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain.
³⁷ Department of Infectious Diseases, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Paris-Est Créteil University, Créteil, France.
³⁸ Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
³⁹ St Vincent's Clinical School, Faculty of Medicine & Health, University of New South Wales, Sydney, New South Wales, Australia.
⁴⁰ Howard Hughes Medical Institute, New York, NY.

^# Contributed equally.

PMID: 36342455
PMCID: PMC9814155
DOI: 10.1084/jem.20220258

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.

Trial registration: ClinicalTrials.gov NCT04402892.

PubMed Disclaimer

Conflict of interest statement

Disclosures: S. Fourati reported personal fees from GSK, Cepheid, and Abbott outside the submitted work. I. Meyts reported grants from CSL Behring outside the submitted work. J.-C. Weill received consulting fees from Institut Mérieux. J.-L. Casanova is an inventor on patent application PCT/US2021/042741, filed July 22, 2021, submitted by The Rockefeller University that covers diagnosis of susceptibility to, and treatment of, viral disease and viral vaccines, including COVID-19 and vaccine-associated diseases. M. Mahévas reported grants from GSK and personal fees from Novartis, LFB, and Amgen outside the submitted work. No other disclosures were reported.

Figures

**Figure 1.**
**mRNA vaccines induce robust humoral responses in patients with type I IFN deficiency. (A)** Overview of the study. **(B)** Evolution of anti–SARS-CoV-2 RBD serum IgG titers after mRNA vaccination. IgG titers (arbitrary units, A.U./ml) are shown according to the time of sampling (d from the second dose) for each patient (left panel) and are then compared between groups at late time point (>120 d, right panel): healthy controls (n = 33 including HD, white circle, n = 29, and YD, green circle), *IRF7*^LOF or *TLR7*^LOF or *IFNAR1*^LOF (purple; *IRF7*^LOF: square, n = 2; *TLR7*^LOF: up triangle, n = 1; *IFNAR1*^LOF down triangle, n = 2), APS-1 (light blue circle, n = 13), and AAB (dark blue circles, n = 8). Late time point was performed at mean 221 d, (range 193–296) for HD at 157 and 197 d for the 2 *IRF7*^LOF patients, 175 d for the *TLR7*^LOF patient, and 142 d for the *IFNAR1*^LOF patient, for APS-1 patients at mean 176 d (range 139–207 d) and for AAB mean 180 d, (range 128–211 d). See Table S1 A. Bars indicate mean ± SEM. **(C)** Evolution of anti–SARS-CoV-2 RBD serum IgA titers after mRNA vaccination. IgA titers (A.U./ml) are shown according to the time of sampling (days) for each patient (left panel) and are then compared between groups at late time point (>120 d, right panel) Dotted line indicates positivity threshold. **(D)** Representative wells for the in vitro neutralization assay of sera against D614G SARS-CoV-2 virus for one patient from each cohort. Dark blue spots represent SARS-CoV-2 infected cells. Top-to-bottom wells show increasing serum dilution (dilution is indicated on the left). **(E and F)** Absence of foci indicate virus neutralization. **(E)** Evolution of IC₅₀ against D614G SARS-CoV-2 after mRNA vaccination of sera tested from HD (n = 31), *IRF7*^LOF/TlR7^LOF/IFNAR1^LOF (n = 3), APS-1 (n = 13), and AAB (n = 8). IC₅₀ (1/dilution) are shown according to the time of sampling (days) for each patient (left panel) and are then compared between groups at late time point (>120 d, right panel). **(F)** Correlation between the anti–SARS-CoV-2 RBD IgG titers at late time point and neutralization potency of the sera at late time point. We performed nonlinear regression in B, C, and E (left panels; semilog line, x is linear, y is log), slopes of the lines are indicated in the boxes; and Kruskal–Wallis with multiple comparisons with Dunn’s Correction in B, C, and E (right panels). All were nonsignificant (P > 0.05). In F, Spearman correlation was performed. P value <0.0001.

**Figure S1.**
**mRNA vaccines induce robust humoral response in patients with type I IFN deficiency. (A)** Heatmap showing the neutralization potency of the patients’ sera against IFN-α-2 and -ω at 100 pg/ml. Each line represents one patient. First column indicates patient group (healthy controls are in green [YD] or white [HD], APS-1 patients are in light blue, patient with *IRF7*^LOF or *TLR7*^LOF in purple, and patient with AAB in dark blue), second line indicates age, and the two last columns indicate sera neutralization. Sera above the positivity threshold (>85%) are depicted in red. Sera below the positivity threshold are depicted in white. **(B)** Schematic representation of type I IFN response theoretically triggered by mRNA vaccines. Steps that are impaired in one of the studied cohorts are indicated in red. NEMO, NF-κB essential modulator; MAVS, mitochondrial antiviral signaling protein; ISG, IFN stimulated genes. **(C)** Longitudinal evolution of anti–SARS-CoV-2 RBD serum IgG titers (A.U./ml) after mRNA vaccination in patients from each cohort according to the day of sampling. Day 0 represents IgG titers after the prime and before the second dose. **(D)** Anti RBD IgG titers (A.U./ml) at late time point (>120 d) according to the age (left panel) or sex (right panel) of the patient. Numbers on the top of the left panel indicate the mean for age group (0–25; 25–65; >65 yr old) and above number indicate the mean for each cohort in each age group. **(E)** Anti RBD IgA titers (A.U./ml) at late time point (>120 d) according to the age (left panel) or sex (right panel) of the patient. Numbers on the top of the left panel indicate the mean for age group (0–25; 25–65; >65 yr-old) and above number indicate the mean for each cohort in each age group. LOD, limit of detection. **(F)** Percentage of ACE2 binding inhibition using competitive ELISA with the sera from the patient at late time point against the ancestral Hu-1 RBD or the Omicron BA.1 RBD. Mean decrease in percentage of inhibition is indicated on the figure. We performed Mann–Whitney in D and E, and Wilcoxon test in F (***P < 0.001, **P < 0.01).

**Figure 2.**
**Circulating MBCs are detected up to 6 mo after mRNA vaccination of patients with type I IFN deficiency. (A)** Representative dot plot of SARS-CoV-2 RBD-staining of CD19⁺IgD⁻CD27⁺CD38^int/⁻ MBCs 30–60 d and >120 d after the second dose in patients representative of each cohort. **(B)** Evolution of percentage of RBD-specific MBCs among CD27⁺IgD⁻MBCs after mRNA vaccination. Frequencies of RBD-specific MBCs are shown according to the time of sampling (days) for each patient (left panel) and are then compared between groups at late time point (>120 d, right panel). Bars indicate mean ± SEM. We performed nonlinear regression in B (semilog line, x is linear, y is log); slopes of the lines are indicated in the box (left panel). Kruskal–Wallis with multiple comparisons with Dunn’s Correction, all nonsignificant (P > 0.05, right panel).

**Figure S2.**
**Circulating MBCs are detected up to 6 mo after mRNA vaccination of patients with type I IFN deficiency. (A)** Flow cytometric gating strategy for the analysis and sorting of SARS-CoV-2 S or RBD-specific MBCs from PBMCs. Lymphocytes were first gated based on morphology, before exclusion of doublets, dead cells, and CD3/CD14 cells. Total CD19⁺ cells were then gated and subdivided into CD38^int/− cells and CD27⁺CD38^hi plasma cells. CD38^int/− B cells were further divided in four quadrants using CD27 and IgD staining. Upper left quadrant defines MBCs, lower left quadrant DN, upper right quadrant CD27⁺IgD⁺ cells, and lower right quadrant naive B cells. SARS-Cov-2 RBD-specific B cells were then analyzed within the B cell population of interest using a His-tagged SARS-Cov-2 RBD protein further revealed by two fluorescently labeled anti-His antibodies. **(B)** Longitudinal evolution of the RBD-specific CD27⁺IgD⁻ MBC (% of CD27⁺IgD⁻ MBCs) in patients from in each cohort. **(C)** Percentage of RBD-specific MBCs at late time point (>120 d) according to the age (left panel) or sex (right panel) of the patient. Numbers on the top of the left panel indicate the mean for age group (0–25; 25–65; >65 yr old) and above numbers indicate the mean for each cohort in each age group. **(D)** Evolution of percentage of RBD-specific DN among CD27⁻IgD⁻DNs after mRNA vaccination. Frequencies of RBD-specific DNs are shown according to the time of sampling (days) for each patient (left panel) and are then compared between groups at late time point (>120 d, right panel). Bars indicate mean ± SEM. **(E)** Percentage of RBD-specific DNs at late time point (>120 d) according to the age (left panel) or sex (right panel) of the patient. Numbers on the top of the left panel indicate the mean for age group (0–25; 25–65; >65 yr old) and above numbers indicate the mean for each cohort in each age group. We performed Mann–Whitney in B, C, and E and nonlinear regression in D (semilog line, x is linear, y is log); slopes of the lines are indicated in the box (left panels). Kruskal–Wallis with multiple comparisons with Dunn’s Correction (right panel). *P < 0.05.

**Figure 3.**
**RBD-specific MBCs are GC derived in patients with type I IFN deficiency. (A–C)** Violin plot showing the number of mutations in the IgV_H of RBD-specific MBCs from (A) HD, (B) *IRF7*^LOF, and (C) *IFNAR1*^LOF subjects. All subjects received two doses of mRNA vaccine. Time point of analysis is however indicated here from the first dose (months), as it represents the first antigen encounter. Each box is a single patient. The pie chart at the top of each plot represents the clonal distribution of RBD-specific MBCs at indicated time points. Colored slices indicate an expanded MBC clone found at several time points from the same donor, gray slices indicate an expanded clone not found at another time point from the same donor, and white slices indicate unique sequences but found at another time point from the same donor. Outer black semicircular line indicates the proportion of sequences belonging to expanded clones. The total number of sequences is indicated at the pie center. **(D)** Mean (± SEM) number of mutations in IgV_H of RBD-specific MBCs for each analyzed patient at a given time point, plotted according to the time of sampling after the first dose. **(E)** Circos plot showing clonal relationships between RBD-specific MBCs from HD (white outer line for HD, green outer line for YD) and patient with impaired IFN signaling (purple for *IRF7*^LOF, *TLR7*^LOF, and *IFNAR*1^LOF, light blue for APS-1) at indicated time point. Inner line indicates clone distribution for each patient and is colored according to the time of sampling. Gray lines indicate public clones shared between patients. We performed Mann–Whitney in A–C (****P < 0.0001) and nonlinear regression with Michaelis–Menten model in D.

**Figure S3.**
**RBD-specific MBCs are GC derived in patients with type I IFN deficiency. (A–D)** Violin plot showing the number of mutations in the IgV_H of RBD-specific MBCs at indicated time point after first dose (months) for YDs (A), IRF7^LOF (B), APS-1 (C), and HD (D). Pie chart at the top of each plot represents the clonal distribution of RBD-specific MBCs at indicated time point. Gray slices indicate expanded clones. Outer black semi-circular line indicates the proportion of sequences belonging to expanded clones. The total number of sequences is indicated at the pie center. We performed Mann–Whitney in B (left).

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

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

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