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

Journal

medRxiv : the preprint server for health sciences
Titre abrégé: medRxiv
Pays: United States
ID NLM: 101767986

Informations de publication

Date de publication:
09 Apr 2021
Historique:
entrez: 14 4 2021
pubmed: 15 4 2021
medline: 15 4 2021
Statut: epublish

Résumé

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. 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 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. 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.

Sections du résumé

BACKGROUND 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 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
RESULTS 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 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.

Identifiants

DOI: 10.1101/2021.04.05.21254656 PMID: 33851176 PMC: PMC8043473
pubmed: 33851176
doi: 10.1101/2021.04.05.21254656
pmc: PMC8043473
pii:
doi:

Types de publication

Preprint

Langues

eng

Subventions

Organisme : NIAID NIH HHS
ID : HHSN272201400008C
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR073752
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI141990
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS106289
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201400006C
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR070155
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA091842
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK109384
Pays : United States
Organisme : NIAID NIH HHS
ID : 75N93019C00051
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK052574
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002345
Pays : United States

Commentaires et corrections

Type : UpdateIn

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Auteurs

Parakkal Deepak (P)

Inflammatory Bowel Diseases Center, Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.

Wooseob Kim (W)

Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.

Michael A Paley (MA)

Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.

Monica Yang (M)

Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.

Alexander B Carvidi (AB)

Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.

Alia A El-Qunni (AA)

Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.

Alem Haile (A)

Clinical Trials Unit, Washington University School of Medicine, St. Louis, MO, USA.

Katherine Huang (K)

Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.

Baylee Kinnett (B)

Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.

Mariel J Liebeskind (MJ)

Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.

Zhuoming Liu (Z)

Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.

Lily E McMorrow (LE)

Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.

Diana Paez (D)

Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.

Dana C Perantie (DC)

Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.

Rebecca E Schriefer (RE)

Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.

Shannon E Sides (SE)

Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.

Mahima Thapa (M)

Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.

Maté Gergely (M)

Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.

Suha Abushamma (S)

Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.

Michael Klebert (M)

Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.

Lynne Mitchell (L)

Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.

Darren Nix (D)

Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.

Jonathan Graf (J)

Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.

Kimberly E Taylor (KE)

Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.

Salim Chahin (S)

Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.

Matthew A Ciorba (MA)

Inflammatory Bowels Diseases Center, Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.

Patricia Katz (P)

Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.

Mehrdad Matloubian (M)

Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.

Jane A O'Halloran (JA)

Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.

Rachel M Presti (RM)

Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.

Gregory F 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.

Sean P J Whelan (SPJ)

Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.

William J Buchser (WJ)

Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.

Lianne S 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.

Mary C 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.

Ali H 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.

Alfred H J 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.

Classifications MeSH