Vaccination with an alkaline extract of Histoplasma capsulatum packaged in glucan particles confers protective immunity in mice.

Autor: Deepe GS Jr; Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267, United States; Veterans Affairs Hospital, Cincinnati, OH 45220, United States. Electronic address: george.deepe@uc.edu., Buesing WR; Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267, United States., Ostroff GR; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, United States., Abraham A; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, United States., Specht CA; Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, United States., Huang H; Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, United States., Levitz SM; Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, United States.
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2018 May 31; Vol. 36 (23), pp. 3359-3367. Date of Electronic Publication: 2018 May 02.
DOI: 10.1016/j.vaccine.2018.04.047
Abstrakt: 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.
(Copyright © 2018 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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