Glucocorticoids and B Cell Depleting Agents Substantially Impair Immunogenicity of mRNA Vaccines to SARS-CoV-2.

Autor:	Deepak P; Inflammatory Bowel Diseases Center, Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA., Kim W; Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA., Paley MA; Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA., Yang M; Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA., Carvidi AB; Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA., El-Qunni AA; Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA., Haile A; Clinical Trials Unit, Washington University School of Medicine, St. Louis, MO, USA., Huang K; Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA., Kinnett B; Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA., Liebeskind MJ; Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA., Liu Z; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA., McMorrow LE; Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA., Paez D; Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA., Perantie DC; Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA., Schriefer RE; Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA., Sides SE; Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA., Thapa M; Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA., Gergely M; Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA., Abushamma S; Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA., Klebert M; Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA., Mitchell L; Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA., Nix D; Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA., Graf J; Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA., Taylor KE; Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA., Chahin S; Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA., Ciorba MA; Inflammatory Bowels Diseases Center, Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA., Katz P; Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA., Matloubian M; Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA., O'Halloran JA; Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA., Presti RM; Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA., Wu GF; Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA; Division of Immunobiology, Department of Pathology and Immunology, Washington, University School of Medicine, St. Louis, MO, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA., Whelan SPJ; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA., Buchser WJ; Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA., Gensler LS; Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA; Arthritis/Immunology Section, San Francisco Veterans Administration Health Care System, San Francisco, CA, USA., Nakamura MC; Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA; Arthritis/Immunology Section, San Francisco Veterans Administration Health Care System, San Francisco, CA, USA., Ellebedy AH; Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA., Kim AHJ; Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2021 Apr 09. Date of Electronic Publication: 2021 Apr 09.
DOI:	10.1101/2021.04.05.21254656
Abstrakt:	Background: Individuals with chronic inflammatory diseases (CID) are frequently treated with immunosuppressive medications that can increase their risk of severe COVID-19. While novel mRNA-based SARS-CoV-2 vaccination platforms provide robust protection in immunocompetent individuals, the immunogenicity in CID patients on immunosuppression is not well established. Therefore, determining the effectiveness of SARS-CoV-2 vaccines in the setting of immunosuppression is essential to risk-stratify CID patients with impaired protection and provide clinical guidance regarding medication management. Methods: We conducted a prospective assessment of mRNA-based vaccine immunogenicity in 133 adults with CIDs and 53 immunocompetent controls. Blood from participants over 18 years of age was collected before initial immunization and 1-2 weeks after the second immunization. Serum anti-SARS-CoV-2 spike (S) IgG + binding, neutralizing antibody titers, and circulating S-specific plasmablasts were quantified to assess the magnitude and quality of the humoral response following vaccination. Results: Compared to immunocompetent controls, a three-fold reduction in anti-S IgG titers (P=0.009) and SARS-CoV-2 neutralization (p<0.0001) were observed in CID patients. B cell depletion and glucocorticoids exerted the strongest effect with a 36- and 10-fold reduction in humoral responses, respectively (p<0.0001). Janus kinase inhibitors and antimetabolites, including methotrexate, also blunted antibody titers in multivariate regression analysis (P<0.0001, P=0.0023, respectively). Other targeted therapies, such as TNF inhibitors, IL-12/23 inhibitors, and integrin inhibitors, had only modest impacts on antibody formation and neutralization. Conclusions: CID patients treated with immunosuppressive therapies exhibit impaired SARS-CoV-2 vaccine-induced immunity, with glucocorticoids and B cell depletion therapy more severely impeding optimal responses.
Databáze:	MEDLINE
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