Vaccine-mediated immune responses to experimental pulmonary Cryptococcus gattii infection in mice.

Vaccine-mediated immune responses to experimental pulmonary Cryptococcus gattii infection in mice.
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DOI:
10.1371/journal.pone.0104316
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Wormley FL Jr
Wormley FL Jr
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chaturvedi AK;Hameed RS;Wozniak KL;Hole CR;Leopold Wager CM;Weintraub ST;Lopez-Ribot JL;Wormley FL Jr

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格特隐球菌是一种真菌病原体,可导致危及生命的呼吸道和传播性感染的免疫能力和免疫抑制的个人。目前,没有针对人类隐球菌病的标准化疫苗,迫切需要有效的治疗和/或疫苗。在这项研究中,我们评估了鼻内免疫的效果与C。gattii细胞壁相关(CW)和/或细胞质(CP)蛋白制剂诱导对实验性肺念珠菌的保护。小鼠的格特感染。用C. gattii CW和/或CP蛋白制剂在用C.加提。保护作用与显著增加的促炎性和Th 1型细胞因子回忆反应有关,在体外和增加C。用C.加提。通过免疫印迹分析,鉴定出许多免疫显性蛋白。使用来自免疫小鼠的血清制备的gattii CW和CP蛋白。用CW和CP蛋白制剂联合免疫导致C.加提。总的来说,我们的研究表明,C。格特氏菌CW和CP蛋白制剂含有抗原,所述抗原可包括在亚单位疫苗中以诱导针对肺C的延长保护。格特感染
Cryptococcus gattii is a fungal pathogen that can cause life-threatening respiratory and disseminated infections in immune-competent and immune-suppressed individuals. Currently, there are no standardized vaccines against cryptococcosis in humans, underlying an urgent need for effective therapies and/or vaccines. In this study, we evaluated the efficacy of intranasal immunization with C. gattii cell wall associated (CW) and/or cytoplasmic (CP) protein preparations to induce protection against experimental pulmonary C. gattii infection in mice. BALB/c mice immunized with C. gattii CW and/or CP protein preparations exhibited a significant reduction in pulmonary fungal burden and prolonged survival following pulmonary challenge with C. gattii. Protection was associated with significantly increased pro-inflammatory and Th1-type cytokine recall responses, in vitro and increased C. gattii-specific antibody production in immunized mice challenged with C. gattii. A number of immunodominant proteins were identified following immunoblot analysis of C. gattii CW and CP protein preparations using sera from immunized mice. Immunization with a combined CW and CP protein preparation resulted in an early increase in pulmonary T cell infiltrates following challenge with C. gattii. Overall, our studies show that C. gattii CW and CP protein preparations contain antigens that may be included in a subunit vaccine to induce prolonged protection against pulmonary C. gattii infection.
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