Vaccination with an alkaline extract of Histoplasma capsulatum packaged in glucan particles confers protective immunity in mice
| Autor: | Stuart M. Levitz, William R. Buesing, George S. Deepe, Charles A. Specht, Gary R. Ostroff, Ambily Abraham, Haibin Huang |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Male medicine.medical_treatment Histoplasma Biology Histoplasmosis Article Microbiology 03 medical and health sciences Interferon-gamma 0302 clinical medicine Immunity medicine Animals Glucans Lung Glucan chemistry.chemical_classification General Veterinary General Immunology and Microbiology Interleukin-17 Public Health Environmental and Occupational Health Cell Differentiation Th1 Cells medicine.disease biology.organism_classification Vaccination Mice Inbred C57BL 030104 developmental biology Infectious Diseases chemistry Immunization Molecular Medicine Th17 Cells Fungal Vaccines Adjuvant Dimorphic fungus 030215 immunology |
| Zdroj: | Vaccine. 36(23) |
| ISSN: | 1873-2518 |
| Popis: | Infection with the dimorphic fungus, Histoplasma capsulatum, occurs world-wide, but North and South America are regions of high endemicity. Interventions to mitigate exposure and consequent disease are limited to remediating a habitat harboring the fungus. The development of a vaccine to prevent infection or lessen its severity is an important advance in disease prevention. Accordingly, we prepared an alkaline extract from the yeast phase of Histoplasma and encased it in glucan particles that act as an adjuvant and delivery vehicle. Immunization of C57BL/6 mice with this encapsulated extract decreased the number of CFUs in lungs and spleens at days 7 and 14 following intranasal infection. Moreover, this vaccine conferred protection against a lethal challenge with the fungus. Cytokine assessment in lungs at a time when the CFUs were similar between controls and vaccinated groups revealed increased quantities of interferon-γ and interleukin-17 in vaccine recipients. This finding was supported by increased generation of both Th1 and Th17 cells in lungs and draining lymph nodes of vaccinated mice compared to controls. Neutralization of interferon-γ or interleukin-17 blunted the effectiveness of vaccination. To identify the proteins comprising this extract, liquid chromatography tandem mass spectrometry was performed. Thus, an H. capsulatum alkaline extract packaged in glucan particles confers protection in an interferon-γ and interleukin-17-dependent manner. Discovery of a single protein or a few proteins in this admixture that mediate protective immunity would represent significant progress in efforts to prevent histoplasmosis. |
| Databáze: | OpenAIRE |
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