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. TITLE=Vaccine Protection of Mice With Primary Immunodeficiencies Against Disseminated Coccidioidomycosis JOURNAL=Frontiers in Cellular and Infection Microbiology VOLUME=11 YEAR=2022 URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.790488 DOI=10.3389/fcimb.2021.790488 ISSN=2235-2988 ABSTRACT=

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.