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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2021.790488/full |
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| author | Daniel A. Powell Daniel A. Powell Amy P. Hsu Christine D. Butkiewicz Hien T. Trinh Jeffrey A. Frelinger Steven M. Holland John N. Galgiani John N. Galgiani Lisa F. Shubitz |
| author_facet | Daniel A. Powell Daniel A. Powell Amy P. Hsu Christine D. Butkiewicz Hien T. Trinh Jeffrey A. Frelinger Steven M. Holland John N. Galgiani John N. Galgiani Lisa F. Shubitz |
| author_sort | Daniel A. Powell |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-11T20:57:35Z |
| format | Article |
| id | doaj.art-a9c4a3a73de04fabae1fce0ea8ad3223 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-04-11T20:57:35Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-a9c4a3a73de04fabae1fce0ea8ad32232022-12-22T04:03:37ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-01-011110.3389/fcimb.2021.790488790488Vaccine Protection of Mice With Primary Immunodeficiencies Against Disseminated CoccidioidomycosisDaniel A. Powell0Daniel A. Powell1Amy P. Hsu2Christine D. Butkiewicz3Hien T. Trinh4Jeffrey A. Frelinger5Steven M. Holland6John N. Galgiani7John N. Galgiani8Lisa F. Shubitz9Valley Fever Center for Excellence, University of Arizona, Tucson, AZ, United StatesDepartment of Immunobiology, University of Arizona, Tucson, AZ, United StatesLaboratory of Clinical and Infectious Diseases, National Institutes of Allergy and Infectious Disease, Bethesda, MD, United StatesValley Fever Center for Excellence, University of Arizona, Tucson, AZ, United StatesValley Fever Center for Excellence, University of Arizona, Tucson, AZ, United StatesValley Fever Center for Excellence, University of Arizona, Tucson, AZ, United StatesLaboratory of Clinical and Infectious Diseases, National Institutes of Allergy and Infectious Disease, Bethesda, MD, United StatesValley Fever Center for Excellence, University of Arizona, Tucson, AZ, United StatesDepartment of Medicine, University of Arizona, Tucson, AZ, United StatesValley Fever Center for Excellence, University of Arizona, Tucson, AZ, United StatesDisseminated 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.https://www.frontiersin.org/articles/10.3389/fcimb.2021.790488/fullcoccidioidomycosisvaccinedisseminatedimmunodeficiencymice |
| spellingShingle | Daniel A. Powell Daniel A. Powell Amy P. Hsu Christine D. Butkiewicz Hien T. Trinh Jeffrey A. Frelinger Steven M. Holland John N. Galgiani John N. Galgiani Lisa F. Shubitz Vaccine Protection of Mice With Primary Immunodeficiencies Against Disseminated Coccidioidomycosis Frontiers in Cellular and Infection Microbiology coccidioidomycosis vaccine disseminated immunodeficiency mice |
| 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 | coccidioidomycosis vaccine disseminated immunodeficiency mice |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2021.790488/full |
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