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首页> 外文期刊>Vaccine >Safety and immunogenicity of a recombinant vaccine against Trypanosoma cruzi in Rhesus macaques
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Safety and immunogenicity of a recombinant vaccine against Trypanosoma cruzi in Rhesus macaques

机译：重组疫苗的安全性和免疫原性对恒河猴克鲁斯瘤瘤中的重组疫苗

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摘要

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi is one of the most important neglected parasitic diseases in the Americas. Vaccines represent an attractive complementary strategy for the control of T. cruzi infection and pre-clinical studies in mice demonstrated that trypomastigote surface antigen (TSA-1) and the flagellar calcium-binding (Tc24) parasite antigens are promising candidates for vaccine development. We performed here the first evaluation of the safety and immunogenicity of two recombinant vaccine antigens (named TSA1-C4 and Tc24-C4) in naive non-human primates. Three rhesus macaques received 3 doses of each recombinant protein, formulated with E6020 (Eisai Co., Ltd.), a novel Toll-like receptor-4 agonist, in a stable emulsion. All parameters from blood chemistry and blood cell counts were stable over the course of the study and unaffected by the vaccine. A specific IgG response against both antigens was detectable after the first vaccine dose, and increased with the second dose. After three vaccine doses, stimulation of PBMCs with a peptide pool derived from TSA1-C4 resulted in the induction of TSA1-C4-specific TNF alpha-, IL-2- and IFN gamma-producing CD4(+) in one or two animals while stimulation with a peptide pool derived from Tc24-C4 only activated IFN gamma-producing CD4(+)T cells in one animal. In two animals there was also activation of TSA1-C4-specific IL2-producing CD8(+) T cells. This is the first report of the immunogenicity of T. cruzi-derived recombinant antigens formulated as an emulsion with a TLR4 agonist in a non-human primate model. Our results strongly support the need for further evaluation of the preventive efficacy of this type of vaccine in non-human primates and explore the effect of the vaccine in a therapeutic model of naturally-infected Chagasic non-human primates, which would strengthen the rationale for the clinical development as a human vaccine against Chagas disease. (C) 2020 Elsevier Ltd. All rights reserved.
机译：查加斯病，由原生动物寄生虫克氏锥虫是美洲最重要的被忽视的寄生虫病之一。疫苗代表一个有吸引力的互补策略锥虫感染的控制和在小鼠中的临床前研究表明，锥鞭毛体表面抗原（TSA-1）和鞭毛钙结合（TC24）寄生虫抗原是疫苗开发的希望的候选。我们在这里执行的安全和两个重组疫苗抗原的幼稚非人类灵长类动物（命名为TSA1-C4和TC24-C4）的免疫原性的第一次评估。三只猕猴接受3个剂量的每种重组蛋白质，与E6020（卫材株式会社），一种新型的Toll样受体4激动剂配制在稳定的乳液。所有的血生化和血液细胞计数参数是在研究的过程中稳定和疫苗的影响。对两种抗原的具体IgG应答是第一疫苗剂量后检测到，并且与第二剂量的增加。经过三个疫苗剂量，与来自TSA1 -C 4衍生的肽库的PBMC的刺激导致TSA1-C4特异性TNFα-的诱导，IL-2-和IFNγ的在一个或两个动物而CD4（+）刺激从TC24-C4的肽池仅激活的IFNγ的CD4（+）T细胞在一个动物。在两只动物也有-C4特定TSA1-IL2的CD8（+）T细胞的活化。这是配制成与在非人类灵长类动物模型中的TLR4激动剂的乳液锥虫来源的重组抗原的免疫原性的第一份报告。我们的研究结果有力地支持了非人类的灵长类动物这类疫苗的预防效果的进一步评估的必要性，并探讨该疫苗的效果自然感染Chagasic非人类灵长类动物的治疗模式，这将加强对基本原理临床开发作为对南美锥虫病的人类疫苗。 （c）2020 elestvier有限公司保留所有权利。

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