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α-Gal 免疫接种可正向影响小鼠模型中心组织中克氏锥虫的定植。

α-Gal immunization positively impacts Trypanosoma cruzi colonization of heart tissue in a mouse model.

机构信息

Universidade Federal de Minas Gerais, Departamento de Parasitologia, Belo Horizonte, Brazil.

Universidad San Martin de Porres, Lima, Peru.

出版信息

PLoS Negl Trop Dis. 2021 Jul 27;15(7):e0009613. doi: 10.1371/journal.pntd.0009613. eCollection 2021 Jul.

Abstract

Chagas disease, caused by the parasite Trypanosoma cruzi, is considered endemic in more than 20 countries but lacks both an approved vaccine and limited treatment for its chronic stage. Chronic infection is most harmful to human health because of long-term parasitic infection of the heart. Here we show that immunization with a virus-like particle vaccine displaying a high density of the immunogenic α-Gal trisaccharide (Qβ-αGal) induced several beneficial effects concerning acute and chronic T. cruzi infection in α1,3-galactosyltransferase knockout mice. Approximately 60% of these animals were protected from initial infection with high parasite loads. Vaccinated animals also produced high anti-αGal IgG antibody titers, improved IFN-γ and IL-12 cytokine production, and controlled parasitemia in the acute phase at 8 days post-infection (dpi) for the Y strain and 22 dpi for the Colombian strain. In the chronic stage of infection (36 and 190 dpi, respectively), all of the vaccinated group survived, showing significantly decreased heart inflammation and clearance of amastigote nests from the heart tissue.

摘要

克氏锥虫引起的恰加斯病被认为流行于 20 多个国家,但缺乏经过批准的疫苗,对其慢性期也仅有有限的治疗方法。慢性感染对人类健康的危害最大,因为它会导致心脏的寄生虫长期感染。在这里,我们展示了一种展示高密度免疫原性α-Gal 三糖(Qβ-αGal)的病毒样颗粒疫苗,该疫苗可诱导α1,3-半乳糖基转移酶敲除小鼠在急性和慢性克氏锥虫感染方面产生多种有益作用。大约 60%的这些动物可以免受高寄生虫负荷的初始感染。接种疫苗的动物还产生了高滴度的抗-αGal IgG 抗体,改善了 IFN-γ 和 IL-12 细胞因子的产生,并控制了 Y 株在感染后 8 天(dpi)和哥伦比亚株在 22 dpi 的急性阶段的寄生虫血症。在感染的慢性阶段(分别为 36 和 190 dpi),所有接种组的动物都存活下来,显示出心脏炎症明显减轻,心脏组织中的无鞭毛体巢明显清除。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b161/8345864/49a0963fdd84/pntd.0009613.g001.jpg

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