Dataset Information

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

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.

SUBMITTER: Deepak P

PROVIDER: S-EPMC8043473 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Publications

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

Deepak Parakkal P Kim Wooseob W Paley Michael A MA Yang Monica M Carvidi Alexander B AB El-Qunni Alia A AA Haile Alem A Huang Katherine K Kinnett Baylee B Liebeskind Mariel J MJ Liu Zhuoming Z McMorrow Lily E LE Paez Diana D Perantie Dana C DC Schriefer Rebecca E RE Sides Shannon E SE Thapa Mahima M Gergely Maté M Abushamma Suha S Klebert Michael M Mitchell Lynne L Nix Darren D Graf Jonathan J Taylor Kimberly E KE Chahin Salim S Ciorba Matthew A MA Katz Patricia P Matloubian Mehrdad M O'Halloran Jane A JA Presti Rachel M RM Wu Gregory F GF Whelan Sean P J SPJ Buchser William J WJ Gensler Lianne S LS Nakamura Mary C MC Ellebedy Ali H AH Kim Alfred H J AHJ

medRxiv : the preprint server for health sciences 20210409

<h4>Background</h4>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-strat ...[more]

PMID: 33851176

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Project description:BackgroundPatients with chronic inflammatory disease (CID) treated with immunosuppressive medications have increased risk for severe COVID-19. Although mRNA-based SARS-CoV-2 vaccination provides protection in immunocompetent persons, immunogenicity in immunosuppressed patients with CID is unclear.ObjectiveTo determine the immunogenicity of mRNA-based SARS-CoV-2 vaccines in patients with CID.DesignProspective observational cohort study.SettingTwo U.S. CID referral centers.ParticipantsVolunteer sample of adults with confirmed CID eligible for early COVID-19 vaccination, including hospital employees of any age and patients older than 65 years. Immunocompetent participants were recruited separately from hospital employees. All participants received 2 doses of mRNA vaccine against SARS-CoV-2 between 10 December 2020 and 20 March 2021. Participants were assessed within 2 weeks before vaccination and 20 days after final vaccination.MeasurementsAnti-SARS-CoV-2 spike (S) IgG+ binding in all participants, and neutralizing antibody titers and circulating S-specific plasmablasts in a subset to assess humoral response after vaccination.ResultsMost of the 133 participants with CID (88.7%) and all 53 immunocompetent participants developed antibodies in response to mRNA-based SARS-CoV-2 vaccination, although some with CID developed numerically lower titers of anti-S IgG. Anti-S IgG antibody titers after vaccination were lower in participants with CID receiving glucocorticoids (n = 17) than in those not receiving them; the geometric mean of anti-S IgG antibodies was 357 (95% CI, 96 to 1324) for participants receiving prednisone versus 2190 (CI, 1598 to 3002) for those not receiving it. Anti-S IgG antibody titers were also lower in those receiving B-cell depletion therapy (BCDT) (n = 10). Measures of immunogenicity differed numerically between those who were and those who were not receiving antimetabolites (n = 48), tumor necrosis factor inhibitors (n = 39), and Janus kinase inhibitors (n = 11); however, 95% CIs were wide and overlapped. Neutralization titers seemed generally consistent with anti-S IgG results. Results were not adjusted for differences in baseline clinical factors, including other immunosuppressant therapies.LimitationsSmall sample that lacked demographic diversity, and residual confounding.ConclusionCompared with nonusers, patients with CID treated with glucocorticoids and BCDT seem to have lower SARS-CoV-2 vaccine-induced antibody responses. These preliminary findings require confirmation in a larger study.Primary funding sourceThe Leona M. and Harry B. Helmsley Charitable Trust, Marcus Program in Precision Medicine Innovation, National Center for Advancing Translational Sciences, and National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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