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

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 immunogeni...

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Detalles Bibliográficos
Autores principales: Deepak, Parakkal, Kim, Wooseob, Paley, Michael A., Yang, Monica, Carvidi, Alexander B., El-Qunni, Alia A., Haile, Alem, Huang, Katherine, Kinnett, Baylee, Liebeskind, Mariel J., Liu, Zhuoming, McMorrow, Lily E., Paez, Diana, Perantie, Dana C., Schriefer, Rebecca E., Sides, Shannon E., Thapa, Mahima, Gergely, Maté, Abushamma, Suha, Klebert, Michael, Mitchell, Lynne, Nix, Darren, Graf, Jonathan, Taylor, Kimberly E., Chahin, Salim, Ciorba, Matthew A., Katz, Patricia, Matloubian, Mehrdad, O’Halloran, Jane A., Presti, Rachel M., Wu, Gregory F., Whelan, Sean P.J., Buchser, William J., Gensler, Lianne S., Nakamura, Mary C., Ellebedy, Ali H., Kim, Alfred H.J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043473/
https://www.ncbi.nlm.nih.gov/pubmed/33851176
http://dx.doi.org/10.1101/2021.04.05.21254656
Descripción
Sumario: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.

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