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Mucosal Heterologous Prime/Boost Vaccination Induces Polyfunctional Systemic Immunity, Improving Protection Against Trypanosoma cruzi.
Frontiers in Immunology ( IF 7.3 ) Pub Date : 2020-01-17 , DOI: 10.3389/fimmu.2020.00128
Andrés Sanchez Alberti 1, 2, 3 , Augusto E Bivona 1, 2 , Marina N Matos 1, 2 , Natacha Cerny 1, 2 , Kai Schulze 3 , Sebastian Weißmann 3 , Thomas Ebensen 3 , Germán González 4 , Celina Morales 4 , Alejandro C Cardoso 1, 2 , Silvia I Cazorla 1, 2 , Carlos A Guzmán 3 , Emilio L Malchiodi 1, 2
Affiliation  

There are several unmet needs in modern immunology. Among them, vaccines against parasitic diseases and chronic infections lead. Trypanosoma cruzi, the causative agent of Chagas disease, is an excellent example of a silent parasitic invasion that affects millions of people worldwide due to its progression into the symptomatic chronic phase of infection. In search for novel vaccine candidates, we have previously introduced Traspain, an engineered trivalent immunogen that was designed to address some of the known mechanisms of T. cruzi immune evasion. Here, we analyzed its performance in different DNA prime/protein boost protocols and characterized the systemic immune response associated with diverse levels of protection. Formulations that include a STING agonist, like c-di-AMP in the boost doses, were able to prime a Th1/Th17 immune response. Moreover, comparison between them showed that vaccines that were able to prime polyfunctional cell-mediated immunity at the CD4 and CD8 compartment enhanced protection levels in the murine model. These findings contribute to a better knowledge of the desired vaccine-elicited immunity against T. cruzi and promote the definition of a vaccine correlate of protection against the infection.



中文翻译:

粘膜异源初免/加强免疫接种可诱导多功能全身免疫,增强对克氏锥虫的保护。

现代免疫学有一些未满足的需求。其中,针对寄生虫病和慢性感染的疫苗是领先的。克氏锥虫恰加斯病的致病因子,是无声寄生虫入侵的一个很好的例子,由于其已发展为有症状的慢性感染阶段,因此影响了全世界数百万人。为了寻找新的候选疫苗,我们先前引入了Traspain,这是一种工程化的三价免疫原,旨在解决某些已知的机制。克鲁斯免疫逃避。在这里,我们分析了其在不同的DNA初免/蛋白质加强方案中的性能,并表征了与多种保护水平相关的全身性免疫应答。包含STING激动剂的制剂(如增强剂量的c-di-AMP)能够引发Th1 / Th17免疫应答。此外,它们之间的比较表明,能够在CD4和CD8区室引发多功能细胞介导的免疫的疫苗增强了鼠模型的保护水平。这些发现有助于更好地了解所需的疫苗诱导的针对克鲁斯 并促进定义针对感染的疫苗相关的疫苗。

更新日期:2020-02-25
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