Vaccine Protection of Mice With Primary Immunodeficiencies Against Disseminated Coccidioidomycosis

Daniel A. Powell, Amy P. Hsu, Christine D. Butkiewicz, Hien T. Trinh, Jeffrey A. Frelinger, Steven M. Holland, John N. Galgiani, Lisa F. Shubitz

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Article number790488
JournalFrontiers in Cellular and Infection Microbiology
Volume11
DOIs
StatePublished - Jan 7 2022

Keywords

  • coccidioidomycosis
  • disseminated
  • immunodeficiency
  • mice
  • vaccine

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

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