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在临床前的口腔查加斯病模型中,鼻内转酸酶疫苗减轻了急性和慢性病理

Maria Florencia Pacini¹, Camila Bulfoni Balbi¹, Brenda Dinatale¹

¹Instituto de Inmunología Clínica y Experimental de Rosario (IDICER-CONICET), Rosario 2000, Argentina.

|October 26, 2024

概括

一种新型的粘膜疫苗使用转酶 (TS) 和c-di-AMP (TS+A) 显示出对夏加斯病的有希望. 在临床前研究中,这种Trypanosoma cruzi候选疫苗减少了寄生虫负载,并预防了急性和慢性心肌病.

科学领域:

免疫学和传染病的研究
疫苗开发疫苗开发
寄生虫学的寄生虫学

背景情况:

查加斯病是由Trypanosoma cruzi引起的,影响全球数百万人,导致30%的病例出现严重的心脏并发症.
目前查加斯病的治疗选择有限,并且没有获得许可的疫苗可用于预防.
查加斯心肌病是一种慢性纤维化疾病,代表了该疾病的最显著和最令人衰弱的表现.

研究的目的:

评估一种针对Trypanosoma cruzi的新型粘膜疫苗候选人的免疫性和预防性疗效.
在临床前模型中评估疫苗对急性和慢性心肌病发展的影响.
调查疫苗引起的免疫反应,包括粘膜和全身免疫.

主要方法:

在小鼠的鼻腔中注射一种包含跨酸酶 (TS) 和c-di-AMP (TS+A) 的疫苗.
评估粘膜 (NALT IgA) 和全身免疫反应 (细胞因子概况,淋巴细胞增殖,DTH).
通过口腔感染的预防疗效的评估T. 克鲁兹,测量寄生虫血症,寄生虫负载,器官损伤和心肌病标志物.

主要成果:

TS+A接种引发了强大的粘膜 (NALT IFN-γ,IL-17a,IL-4 mRNA,IgA) 和全身免疫反应 (Th1/Th2/Th17细胞因子,DTH).
接种疫苗的小鼠在感染后显著减少了寄生虫血症和心脏,肌肉和肠道中的寄生虫负担.
通过减少TGF-β等亲纤维性标志物,TS+A显著减轻了急性心肌炎和慢性心肌病,包括纤维化和心电图异常.

结论:

一种基于跨酸酶 (TS) 和c-di-AMP (TS+A) 的粘膜疫苗是预防T.的可行策略. 克鲁兹的感染.
这种候选疫苗有效地减少了寄生虫负载,并防止了查加斯心肌病的发展,这是主要的疾病并发症.
这项研究表明,TS+A作为一种有前途的粘膜疫苗,有潜力控制查加斯病及其心脏后果.

关键词:

试osoma cruzi 是一种类型的虫.c-di-AMP 的时间.慢性查加斯心肌病查加斯心肌病鼻接种疫苗鼻接种疫苗口腔查加斯病查加斯病是什么跨-化酶的使用.

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