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

  

View ORCID ProfileParakkal Deepak, Wooseob Kim,  View ORCID ProfileMichael A. Paley,  View ORCID ProfileMonica Yang, Alexander B. Carvidi,  View ORCID ProfileAlia A. El-Qunni, Alem Haile,  View ORCID ProfileKatherine Huang, Baylee Kinnett, Mariel J. Liebeskind, Zhuoming Liu,  View ORCID ProfileLily E. McMorrow, Diana Paez,  View ORCID ProfileDana C. Perantie,  View ORCID ProfileRebecca E. Schriefer, Shannon E. Sides, Mahima Thapa, Maté Gergely, Suha Abushamma, Michael Klebert, Lynne Mitchell, Darren Nix, Jonathan Graf,  View ORCID ProfileKimberly E. Taylor,  View ORCID ProfileSalim Chahin,  View ORCID ProfileMatthew A. Ciorba,  View ORCID ProfilePatricia Katz,  View ORCID ProfileMehrdad Matloubian,  View ORCID ProfileJane A. O’Halloran,  View ORCID ProfileRachel M. Presti,  View ORCID ProfileGregory F. Wu,  View ORCID ProfileSean P.J. Whelan,  View ORCID ProfileWilliam J. Buchser,  View ORCID ProfileLianne S. Gensler,  View ORCID ProfileMary C. Nakamura,  View ORCID ProfileAli H. Ellebedy,  View ORCID ProfileAlfred H.J. Kim

doi: https://doi.org/10.1101/2021.04.05.21254656

This article is a preprint and has not been peer-reviewed [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.04.05.21254656v2.full.pdf

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 (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.

Competing Interest Statement

P.D. participated in consulting, advisory board, or speaker's bureau for Janssen, Pfizer, Prometheus Biosciences, Boehringer Ingelheim, AbbVie, and Arena Pharmaceuticals and received funding under a sponsored research agreement unrelated to the data in the paper from Takeda Pharmaceutical, Arena Pharmaceuticals, Bristol Myers Squibb-Celgene, and Boehringer Ingelheim. M.A.C. participated in consulting, advisory board, or speaker's bureau for AbbVie, Pfizer, Bristol Myers Squibb, and Theravance, and received funding under a sponsored research agreement unrelated to the data in the paper from Incyte, Pfizer, Janssen, and the Crohn's and Colitis Foundation. G.F.W. received honoraria for consulting for Novartis and Genentech and funding under a sponsored research agreement unrelated to the data in the paper from Biogen, EMD Serono, and Roche. The S.P.J.L. laboratory received funding under a sponsored research agreement unrelated to the data in the paper from Vir Biotechnology, AbbVie, and SAb therapeutics. L.S.G. received honoraria for consulting for AbbVie, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB received funding under a sponsored research agreement unrelated to the data in the paper from Pfizer and UCB. The A.H.E. laboratory received funding under a sponsored research agreement unrelated to the data in the paper from Emergent BioSolutions and Abbvie. A.H.J.K. participated in consulting, advisory board, or speaker's bureau for Alexion Pharmaceuticals, Aurinia Pharmaceuticals, Annexon Biosciences, Exagen Diagnostics, Inc., and GlaxoSmithKilne and received funding under a sponsored research agreement unrelated to the data in the paper from GlaxoSmithKline. All other authors declare no competing interests.

Funding Statement

This research was supported by The Leona M. and Harry B. Helmsley Charitable Trust, Washington University Digestive Disease Research Core Center (NIDDK P30DK052574), Washington University Rheumatic Diseases Research Resource-Based Center (NIAMS P30AR073752), The Judy Miniace Research Fund for the Washington University Lupus Clinic, and UCSF investigators were funded by PREMIER, a NIAMS P30 Center (P30AR070155) and the Russell/Engleman Rheumatology Research Center. This study utilized samples obtained from the Washington University School of Medicine's COVID-19 biorepository, which is supported by the Barnes-Jewish Hospital Foundation, the Siteman Cancer Center grant P30CA091842 from the National Cancer Institute of the National Institutes of Health, and the Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from the National Center for Advancing Translational Sciences of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the view of the NIH.

https://www.medrxiv.org/content/10.1101/2021.04.05.21254656v2