University of California San Francisco
UCSF School of Medicine UCSF Medical Center

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

medRxiv : the preprint server for health sciences
2021
https://researcherprofiles.org/profile/192088091
33851176
Deepak P, Kim W, Paley MA, Yang M, Carvidi AB, El-Qunni AA, Haile A, Huang K, Kinnett B, Liebeskind MJ, Liu Z, McMorrow LE, Paez D, Perantie DC, Schriefer RE, Sides SE, Thapa M, Gergely M, Abushamma S, Klebert M, Mitchell L, Nix D, Graf J, Taylor KE, Chahin S, Ciorba MA, Katz P, Matloubian M, O'Halloran JA, Presti RM, Wu GF, Whelan SPJ, Buchser WJ, Gensler LS, Nakamura MC, Ellebedy AH, Kim AHJ
Abstract

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 (p0.0001) 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 (p0.0001). Janus kinase inhibitors and antimetabolites, including methotrexate, also blunted antibody titers in multivariate regression analysis (P0.0001, 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.