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Vaccine Protection of Mice With Primary Immunodeficiencies Against Disseminated Coccidioidomycosis

Disseminated coccidioidomycosis (DCM), often a severe and refractory disease leading to poor outcomes, is a risk for people with certain primary immunodeficiencies (PID). Several DCM-associated PID (STAT4, STAT3, IFNγ, and Dectin-1) are modeled in mice. To determine if vaccination could provide thes...

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Autores principales: Powell, Daniel A., Hsu, Amy P., Butkiewicz, Christine D., Trinh, Hien T., Frelinger, Jeffrey A., Holland, Steven M., Galgiani, John N., Shubitz, Lisa F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8777018/
https://www.ncbi.nlm.nih.gov/pubmed/35071044
http://dx.doi.org/10.3389/fcimb.2021.790488
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author Powell, Daniel A.
Hsu, Amy P.
Butkiewicz, Christine D.
Trinh, Hien T.
Frelinger, Jeffrey A.
Holland, Steven M.
Galgiani, John N.
Shubitz, Lisa F.
author_facet Powell, Daniel A.
Hsu, Amy P.
Butkiewicz, Christine D.
Trinh, Hien T.
Frelinger, Jeffrey A.
Holland, Steven M.
Galgiani, John N.
Shubitz, Lisa F.
author_sort Powell, Daniel A.
collection PubMed
description Disseminated coccidioidomycosis (DCM), often a severe and refractory disease leading to poor outcomes, is a risk for people with certain primary immunodeficiencies (PID). Several DCM-associated PID (STAT4, STAT3, IFNγ, and Dectin-1) are modeled in mice. To determine if vaccination could provide these mice protection, mice with mutations in Stat4, Stat3, Ifngr1, Clec7a (Dectin-1), and Rag-1 (T- and B-cell deficient) knockout (KO) mice were vaccinated with the live, avirulent, Δcps1 vaccine strain and subsequently challenged intranasally with pathogenic Coccidioides posadasii Silveira strain. Two weeks post-infection, vaccinated mice of all strains except Rag-1 KO had significantly reduced lung and spleen fungal burdens (p<0.05) compared to unvaccinated control mice. Splenic dissemination was prevented in most vaccinated immunodeficient mice while all unvaccinated B6 mice and the Rag-1 KO mice displayed disseminated disease. The mitigation of DCM by Δcps1 vaccination in these mice suggests that it could also benefit humans with immunogenetic risks of severe disease.
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spelling pubmed-87770182022-01-22 Vaccine Protection of Mice With Primary Immunodeficiencies Against Disseminated Coccidioidomycosis Powell, Daniel A. Hsu, Amy P. Butkiewicz, Christine D. Trinh, Hien T. Frelinger, Jeffrey A. Holland, Steven M. Galgiani, John N. Shubitz, Lisa F. Front Cell Infect Microbiol Cellular and Infection Microbiology Disseminated coccidioidomycosis (DCM), often a severe and refractory disease leading to poor outcomes, is a risk for people with certain primary immunodeficiencies (PID). Several DCM-associated PID (STAT4, STAT3, IFNγ, and Dectin-1) are modeled in mice. To determine if vaccination could provide these mice protection, mice with mutations in Stat4, Stat3, Ifngr1, Clec7a (Dectin-1), and Rag-1 (T- and B-cell deficient) knockout (KO) mice were vaccinated with the live, avirulent, Δcps1 vaccine strain and subsequently challenged intranasally with pathogenic Coccidioides posadasii Silveira strain. Two weeks post-infection, vaccinated mice of all strains except Rag-1 KO had significantly reduced lung and spleen fungal burdens (p<0.05) compared to unvaccinated control mice. Splenic dissemination was prevented in most vaccinated immunodeficient mice while all unvaccinated B6 mice and the Rag-1 KO mice displayed disseminated disease. The mitigation of DCM by Δcps1 vaccination in these mice suggests that it could also benefit humans with immunogenetic risks of severe disease. Frontiers Media S.A. 2022-01-07 /pmc/articles/PMC8777018/ /pubmed/35071044 http://dx.doi.org/10.3389/fcimb.2021.790488 Text en Copyright © 2022 Powell, Hsu, Butkiewicz, Trinh, Frelinger, Holland, Galgiani and Shubitz https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Powell, Daniel A.
Hsu, Amy P.
Butkiewicz, Christine D.
Trinh, Hien T.
Frelinger, Jeffrey A.
Holland, Steven M.
Galgiani, John N.
Shubitz, Lisa F.
Vaccine Protection of Mice With Primary Immunodeficiencies Against Disseminated Coccidioidomycosis
title Vaccine Protection of Mice With Primary Immunodeficiencies Against Disseminated Coccidioidomycosis
title_full Vaccine Protection of Mice With Primary Immunodeficiencies Against Disseminated Coccidioidomycosis
title_fullStr Vaccine Protection of Mice With Primary Immunodeficiencies Against Disseminated Coccidioidomycosis
title_full_unstemmed Vaccine Protection of Mice With Primary Immunodeficiencies Against Disseminated Coccidioidomycosis
title_short Vaccine Protection of Mice With Primary Immunodeficiencies Against Disseminated Coccidioidomycosis
title_sort vaccine protection of mice with primary immunodeficiencies against disseminated coccidioidomycosis
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8777018/
https://www.ncbi.nlm.nih.gov/pubmed/35071044
http://dx.doi.org/10.3389/fcimb.2021.790488
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