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表达Gp43的酿酒酵母可保护小鼠免受巴西副球孢子菌感染。

Saccharomyces cerevisiae expressing Gp43 protects mice against Paracoccidioides brasiliensis infection.

作者信息

Assis-Marques Mariana Aprigio, Oliveira Aline Ferreira, Ruas Luciana Pereira, dos Reis Thaila Fernanda, Roque-Barreira Maria Cristina, Coelho Paulo Sergio Rodrigues

机构信息

Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, Ribeirão Preto, SP, 14049-900, Brasil.

出版信息

PLoS One. 2015 Mar 19;10(3):e0120201. doi: 10.1371/journal.pone.0120201. eCollection 2015.

Abstract

The dimorphic fungus Paracoccidioides brasiliensis is the etiological agent of paracoccidioidomycosis (PCM). It is believed that approximately 10 million people are infected with the fungus and approximately 2% will eventually develop the disease. Unlike viral and bacterial diseases, fungal diseases are the ones against which there is no commercially available vaccine. Saccharomyces cerevisiae may be a suitable vehicle for immunization against fungal infections, as they require the stimulation of different arms of the immune response. Here we evaluated the efficacy of immunizing mice against PCM by using S. cerevisiae yeast expressing gp43. When challenged by inoculation of P. brasiliensis yeasts, immunized animals showed a protective profile in three different assays. Their lung parenchyma was significantly preserved, exhibiting fewer granulomas with fewer fungal cells than found in non-immunized mice. Fungal burden was reduced in the lung and spleen of immunized mice, and both organs contained higher levels of IL-12 and IFN-γ compared to those of non-vaccinated mice, a finding that suggests the occurrence of Th1 immunity. Taken together, our results indicate that the recombinant yeast vaccine represents a new strategy to confer protection against PCM.

摘要

双相真菌巴西副球孢子菌是副球孢子菌病(PCM)的病原体。据信约有1000万人感染了这种真菌,其中约2%最终会发病。与病毒和细菌疾病不同,真菌疾病尚无市售疫苗。酿酒酵母可能是用于真菌感染免疫的合适载体,因为它们需要刺激免疫反应的不同分支。在此,我们评估了使用表达gp43的酿酒酵母对小鼠进行PCM免疫的效果。当通过接种巴西副球孢子菌酵母进行攻击时,免疫动物在三种不同的试验中表现出保护作用。它们的肺实质得到显著保护,与未免疫小鼠相比,肉芽肿更少,真菌细胞也更少。免疫小鼠的肺和脾中的真菌负荷降低,与未接种疫苗的小鼠相比,这两个器官中IL-12和IFN-γ的水平更高,这一发现表明发生了Th1免疫。综上所述,我们的结果表明重组酵母疫苗是一种针对PCM提供保护的新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8cc/4366343/8844b9eb029f/pone.0120201.g001.jpg

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