Chagas disease (ChD), caused by the hemoflagellate parasite Trypanosoma cruzi, affects six to seven million people in Latin America. Lately, it has become an emerging public health concern in nonendemic regions such as North America and Europe. There is no prophylactic or therapeutic vaccine as yet, and current chemotherapy is rather toxic and has limited efficacy in the chronic phase of the disease. The parasite surface is heavily coated by glycoproteins such as glycosylphosphatidylinositol (GPI)-anchored mucins (tGPI-mucins), which display highly immunogenic terminal nonreducing α-galactopyranosyl (α-Gal)-containing glycotopes that are entirely absent in humans. The immunodominant tGPI-mucin α-Gal glycotope, the trisaccharide Galα1,3Galβ1,4GlcNAc (Galα3LN), elicits high levels of protective T. cruzi-specific anti-α-Gal antibodies in ChD patients in both the acute and chronic phases. Although glycoconjugates are the major parasite glycocalyx antigens, they remain completely unexplored as potential ChD vaccine candidates. Here we investigate the efficacy of the T. cruzi immunodominant glycotope Galα3LN, covalently linked to a carrier protein (human serum albumin (HSA)), as a prophylactic vaccine candidate in the acute model of ChD, using the α1,3-galactosyltransferase-knockout (α1,3GalT-KO) mouse, which mimics the human immunoresponse to α-Gal glycotopes. Animals vaccinated with Galα3LN-HSA were fully protected against lethal T. cruzi challenge by inducing a strong anti-α-Gal antibody-mediated humoral response. Furthermore, Galα3LN-HSA-vaccinated α1,3GalT-KO mice exhibited significant reduction (91.7–99.9%) in parasite load in all tissues analyzed, cardiac inflammation, myocyte necrosis, and T cell infiltration. This is a proof-of-concept study to demonstrate the efficacy of a prophylactic α-Gal-based glycovaccine for experimental acute Chagas disease.

查加斯病（冠心病），引起hemoflagellate寄生虫克氏锥虫，影响了拉美六到七万人。最近，它已成为北美和欧洲等非流行地区日益关注的公共卫生问题。尚无预防性或治疗性疫苗，目​​前的化学疗法毒性很大，并且在该疾病的慢性期疗效有限。寄生虫表面被糖蛋白如糖基磷脂酰肌醇（GPI）锚定的粘蛋白（tGPI-粘蛋白）大量覆盖，这些蛋白显示出高度免疫原性的末端非还原性含α-半乳糖吡喃糖基（α-Gal）的糖基，而这些糖基在人体中是完全不存在的。免疫优势的tGPI-粘蛋白α-Gal糖基三糖Galα1,3Galβ1,4GlcNAc（Galα3LN）引起高水平的保护性T。在急性期和慢性期的ChD患者中均具有cruzi特异的抗α-Gal抗体。尽管糖缀合物是主要的寄生虫糖萼抗原，但它们仍未完全开发为潜在的ChD疫苗候选者。在这里，我们研究了T的功效。克氏锥虫免疫糖表位Galα3LN，共价连接到载体蛋白（人血清白蛋白（HSA）），如冠心病的急性模型中预防疫苗候选，使用α1,3半乳糖转移酶敲除（α1,3GalT-KO）小鼠，模仿人类对α-Gal糖基的免疫反应。接种了Galα3LN-HSA的动物受到了致命T的完全保护。克鲁兹通过诱导强烈的抗α-Gal抗体介导的体液反应来应对这一挑战。此外，接种了Galα3LN-HSA的α1,3GalT-KO小鼠在所有分析的组织，心脏炎症，心肌细胞坏死和T细胞浸润中的寄生虫负荷均显着降低（91.7–99.9％）。这是一项概念验证研究，旨在证明预防性基于α-Gal的糖疫苗对实验性急性恰加斯病的功效。