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A Heat-Killed Mutant Strain Induces Host Protection against Multiple Invasive Mycoses in a Murine Vaccine Model.

著者 Wang Y , Wang K , Masso-Silva JA , Rivera A , Xue C
MBio.2019 Nov 26 ; 10(6):.
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is a fungal pathogen that infects the lungs and then often disseminates to the central nervous system, causing meningitis. How is able to suppress host immunity and escape the antifungal activity of macrophages remains incompletely understood. We reported that the F-box protein Fbp1, a subunit of the SCF(Fbp1) E3 ligase, promotes virulence by regulating host- interactions. Our recent studies demonstrated that the Δ mutant elicited superior protective Th1 host immunity in the lungs and that the enhanced immunogenicity of heat-killed Δ yeast cells can be harnessed to confer protection against a subsequent infection with the virulent parental strain. We therefore examined the use of heat-killed Δ cells in several vaccination strategies. Interestingly, the vaccine protection remains effective even in mice depleted of CD4 T cells. This finding is particularly important in the context of HIV/AIDS-induced immune deficiency. Moreover, we observed that vaccinating mice with heat-killed Δ induces significant cross-protection against challenge with diverse invasive fungal pathogens, including , , and , as well as partial protection against Thus, our data suggest that the heat-killed strain has the potential to be a suitable vaccine candidate against cryptococcosis and other invasive fungal infections in both immunocompetent and immunocompromised populations. Invasive fungal infections kill more than 1.5 million people each year, with limited treatment options. There is no vaccine available in clinical use to prevent and control fungal infections. Our recent studies showed that a mutant of the F-box protein Fbp1, a subunit of the SCF(Fbp1) E3 ligase in , elicited superior protective Th1 host immunity. Here, we demonstrate that the heat-killed Δ cells (HK-fbp1) can be harnessed to confer protection against a challenge by the virulent parental strain, even in animals depleted of CD4 T cells. This finding is particularly important in the context of HIV/AIDS-induced immune deficiency. Moreover, we observed that HK-fbp1 vaccination induces significant cross-protection against challenge with diverse invasive fungal pathogens. Thus, our data suggest that HK-fbp1 has the potential to be a broad-spectrum vaccine candidate against invasive fungal infections in both immunocompetent and immunocompromised populations.
PMID: 31772051 [PubMed - in process]
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