Disease-associated B cells and immune endotypes shape adaptive immune responses to SARS-CoV-2 mRNA vaccination in human SLE.
| Title: | Disease-associated B cells and immune endotypes shape adaptive immune responses to SARS-CoV-2 mRNA vaccination in human SLE. |
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| Authors: | Faliti CE; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA.; Emory Autoimmunity Center of Excellence, Emory University, Atlanta, GA, USA.; Van TTP; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA.; Emory Autoimmunity Center of Excellence, Emory University, Atlanta, GA, USA.; Anam FA; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA.; Emory Autoimmunity Center of Excellence, Emory University, Atlanta, GA, USA.; Cheedarla N; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.; Williams ME; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA.; Mishra AK; Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Silver Spring, MD, USA.; Usman SY; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA.; Emory Autoimmunity Center of Excellence, Emory University, Atlanta, GA, USA.; Woodruff MC; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA.; Emory Autoimmunity Center of Excellence, Emory University, Atlanta, GA, USA.; Kraker G; Dotmatics, Inc., Boston, MA, USA.; Runnstrom MC; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University, Atlanta, GA, USA.; Kyu S; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University, Atlanta, GA, USA.; Sanz D; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA.; Emory Autoimmunity Center of Excellence, Emory University, Atlanta, GA, USA.; Ahmed H; Department of Biology, Emory University, Atlanta, GA, USA.; Ghimire M; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA.; Emory Autoimmunity Center of Excellence, Emory University, Atlanta, GA, USA.; Morrison-Porter A; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University, Atlanta, GA, USA.; Quehl H; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University, Atlanta, GA, USA.; Haddad NS; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University, Atlanta, GA, USA.; MicroB-plex, Inc., Atlanta, GA, USA.; Chen W; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA.; Emory Autoimmunity Center of Excellence, Emory University, Atlanta, GA, USA.; Cheedarla S; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.; Neish AS; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.; Roback JD; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.; Antia R; Department of Biology, Emory University, Atlanta, GA, USA.; Hom J; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA.; Emory Autoimmunity Center of Excellence, Emory University, Atlanta, GA, USA.; Tipton CM; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA.; Emory Autoimmunity Center of Excellence, Emory University, Atlanta, GA, USA.; Lindner JM; BioMed X Institute, Heidelberg, Germany.; Ghosn E; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA.; Khurana S; Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Silver Spring, MD, USA.; Scharer CD; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA.; Khosroshahi A; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA.; Emory Autoimmunity Center of Excellence, Emory University, Atlanta, GA, USA.; Lee FE; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University, Atlanta, GA, USA.; Sanz I; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA. Ignacio.sanz@emory.edu.; Emory Autoimmunity Center of Excellence, Emory University, Atlanta, GA, USA. Ignacio.sanz@emory.edu. |
| Source: | Nature immunology [Nat Immunol] 2025 Jan; Vol. 26 (1), pp. 131-145. Date of Electronic Publication: 2024 Nov 12. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Nature America Inc Country of Publication: United States NLM ID: 100941354 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1529-2916 (Electronic) Linking ISSN: 15292908 NLM ISO Abbreviation: Nat Immunol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: New York, NY : Nature America Inc. c2000- |
| MeSH Terms: | Lupus Erythematosus, Systemic*/immunology ; SARS-CoV-2*/immunology ; COVID-19*/immunology ; COVID-19*/prevention & control ; Spike Glycoprotein, Coronavirus*/immunology ; Antibodies, Viral*/immunology ; COVID-19 Vaccines*/immunology ; B-Lymphocytes*/immunology; Antibodies, Neutralizing/immunology ; Antibodies, Monoclonal, Humanized/therapeutic use ; mRNA Vaccines/immunology ; Humans ; Female ; Adaptive Immunity ; Adult ; Middle Aged ; Male ; Vaccination ; Immunologic Memory |
| Abstract: | Severe acute respiratory syndrome coronavirus 2 mRNA vaccination has reduced effectiveness in certain immunocompromised individuals. However, the cellular mechanisms underlying these defects, as well as the contribution of disease-induced cellular abnormalities, remain largely unexplored. In this study, we conducted a comprehensive serological and cellular analysis of patients with autoimmune systemic lupus erythematosus (SLE) who received the Wuhan-Hu-1 monovalent mRNA coronavirus disease 2019 vaccine. Our findings revealed that patients with SLE exhibited reduced avidity of anti-receptor-binding domain antibodies, leading to decreased neutralization potency and breadth. We also observed a sustained anti-spike response in IgD-CD27- 'double-negative (DN)' DN2/DN3 B cell populations persisting during memory responses and with greater representation in the SLE cohort. Additionally, patients with SLE displayed compromised anti-spike T cell immunity. Notably, low vaccine efficacy strongly correlated with higher values of a newly developed extrafollicular B and T cell score, supporting the importance of distinct B cell endotypes. Finally, we found that anti-BAFF blockade through belimumab treatment was associated with poor vaccine immunogenicity due to inhibition of naive B cell priming and an unexpected impact on circulating T follicular helper cells.; (© 2024. The Author(s).) |
| Competing Interests: | Competing interests: F.E.-H.L. is the founder of MicroB-plex, Inc., and has research grants with Genentech. I.S. has research grants with Glaxo Smith Kline. The other authors declare no competing interests. |
| Comments: | Erratum in: Nat Immunol. 2025 Jan;26(1):148. doi: 10.1038/s41590-024-02045-y.. (PMID: 39622950) |
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| Grant Information: | U19-AI110483 Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID); U54- 762 CA260563-01 Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID); P01 AI125180 United States AI NIAID NIH HHS; GCBER008 U.S. Department of Health & Human Services | U.S. Food and Drug Administration (U.S. Food & Drug Administration); U54 CA260563 United States CA NCI NIH HHS; GCBER005 U.S. Department of Health & Human Services | U.S. Food and Drug Administration (U.S. Food & Drug Administration); U19 AI110483 United States AI NIAID NIH HHS |
| Substance Nomenclature: | 0 (Spike Glycoprotein, Coronavirus); 0 (Antibodies, Viral); 0 (COVID-19 Vaccines); 0 (spike protein, SARS-CoV-2); 0 (Antibodies, Neutralizing); 73B0K5S26A (belimumab); 0 (Antibodies, Monoclonal, Humanized); 0 (mRNA Vaccines) |
| Entry Date(s): | Date Created: 20241112 Date Completed: 20250103 Latest Revision: 20260306 |
| Update Code: | 20260306 |
| PubMed Central ID: | PMC11695260 |
| DOI: | 10.1038/s41590-024-02010-9 |
| PMID: | 39533072 |
| Database: | MEDLINE |
Journal Article