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Modulation of immunosuppressant drug treatment to improve SARS-CoV-2 vaccine efficacy in mice

The COVID-19 pandemic dramatically demonstrated the need for improved vaccination strategies and therapeutic responses to combat infectious diseases. However, the efficacy of vaccines has not yet been demonstrated in combination with commonly used immunosuppressive drug regimens. We sought to determ...

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Autores principales: Paschall, Amy V., Ozdilek, Ahmet, Briner, Sydney L., Brindley, Melinda A., Avci, Fikri Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Ltd. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718886/
https://www.ncbi.nlm.nih.gov/pubmed/34991929
http://dx.doi.org/10.1016/j.vaccine.2021.12.058
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author Paschall, Amy V.
Ozdilek, Ahmet
Briner, Sydney L.
Brindley, Melinda A.
Avci, Fikri Y.
author_facet Paschall, Amy V.
Ozdilek, Ahmet
Briner, Sydney L.
Brindley, Melinda A.
Avci, Fikri Y.
author_sort Paschall, Amy V.
collection PubMed
description The COVID-19 pandemic dramatically demonstrated the need for improved vaccination strategies and therapeutic responses to combat infectious diseases. However, the efficacy of vaccines has not yet been demonstrated in combination with commonly used immunosuppressive drug regimens. We sought to determine how common pharmaceutical drugs used in autoimmune disorders can alter immune responses to the SARS-CoV-2 spike protein vaccination. We treated mice with five immunosuppressant drugs (cyclophosphamide, leflunomide, methotrexate, methylprednisolone, and mycophenolate mofetil), each with various mechanisms of action prior to and following immunization with SARS-CoV-2 spike protein. We assessed the functionality of antibody responses to spike protein and compared immune cell populations in mice that received no treatment with those that received continuous or temporarily suspended immune suppressive therapy. All tested immunosuppressants significantly reduced the antibody titers in serum and functional antibody response against SARS-CoV-2 spike protein in immunized mice. Temporarily halting selected immunosuppressants (methylprednisolone and methotrexate, but not cyclophosphamide) improved antibody responses significantly. Through proof-of-principle experiments utilizing a mouse model, we demonstrated that immune suppression in autoimmune disorders through pharmaceutical treatments may impair vaccine response to SARS-CoV-2, and temporary suspension of immunosuppressant treatment may be necessary to mount an effective antibody vaccine response. This work provides feasibility for future clinical assessment of the impact of immunosuppressants on vaccine efficacy in humans.
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spelling pubmed-87188862022-01-03 Modulation of immunosuppressant drug treatment to improve SARS-CoV-2 vaccine efficacy in mice Paschall, Amy V. Ozdilek, Ahmet Briner, Sydney L. Brindley, Melinda A. Avci, Fikri Y. Vaccine Article The COVID-19 pandemic dramatically demonstrated the need for improved vaccination strategies and therapeutic responses to combat infectious diseases. However, the efficacy of vaccines has not yet been demonstrated in combination with commonly used immunosuppressive drug regimens. We sought to determine how common pharmaceutical drugs used in autoimmune disorders can alter immune responses to the SARS-CoV-2 spike protein vaccination. We treated mice with five immunosuppressant drugs (cyclophosphamide, leflunomide, methotrexate, methylprednisolone, and mycophenolate mofetil), each with various mechanisms of action prior to and following immunization with SARS-CoV-2 spike protein. We assessed the functionality of antibody responses to spike protein and compared immune cell populations in mice that received no treatment with those that received continuous or temporarily suspended immune suppressive therapy. All tested immunosuppressants significantly reduced the antibody titers in serum and functional antibody response against SARS-CoV-2 spike protein in immunized mice. Temporarily halting selected immunosuppressants (methylprednisolone and methotrexate, but not cyclophosphamide) improved antibody responses significantly. Through proof-of-principle experiments utilizing a mouse model, we demonstrated that immune suppression in autoimmune disorders through pharmaceutical treatments may impair vaccine response to SARS-CoV-2, and temporary suspension of immunosuppressant treatment may be necessary to mount an effective antibody vaccine response. This work provides feasibility for future clinical assessment of the impact of immunosuppressants on vaccine efficacy in humans. Elsevier Ltd. 2022-02-07 2021-12-31 /pmc/articles/PMC8718886/ /pubmed/34991929 http://dx.doi.org/10.1016/j.vaccine.2021.12.058 Text en © 2021 Elsevier Ltd. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Paschall, Amy V.
Ozdilek, Ahmet
Briner, Sydney L.
Brindley, Melinda A.
Avci, Fikri Y.
Modulation of immunosuppressant drug treatment to improve SARS-CoV-2 vaccine efficacy in mice
title Modulation of immunosuppressant drug treatment to improve SARS-CoV-2 vaccine efficacy in mice
title_full Modulation of immunosuppressant drug treatment to improve SARS-CoV-2 vaccine efficacy in mice
title_fullStr Modulation of immunosuppressant drug treatment to improve SARS-CoV-2 vaccine efficacy in mice
title_full_unstemmed Modulation of immunosuppressant drug treatment to improve SARS-CoV-2 vaccine efficacy in mice
title_short Modulation of immunosuppressant drug treatment to improve SARS-CoV-2 vaccine efficacy in mice
title_sort modulation of immunosuppressant drug treatment to improve sars-cov-2 vaccine efficacy in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718886/
https://www.ncbi.nlm.nih.gov/pubmed/34991929
http://dx.doi.org/10.1016/j.vaccine.2021.12.058
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