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作为潜在的活疫苗,共同表达针对实验性皮肤利什曼病的不同唾液腺蛋白,在 BALB/c 小鼠模型中。

as Potential Live Vaccine Co-Expressing Distinct Salivary Gland Proteins Against Experimental Cutaneous Leishmaniasis in BALB/c Mice Model.

机构信息

Department of Medical Biotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.

Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, Tehran, Iran.

出版信息

Front Immunol. 2022 Jun 10;13:895234. doi: 10.3389/fimmu.2022.895234. eCollection 2022.

Abstract

Leishmaniasis is a neglected vector-borne disease caused by parasites transmitted through the infected sand flies bite. Current treatments are limited, partly due to their high cost and significant adverse effects, and no human vaccine is yet available. Sand flies saliva has been examined for their potential application as an anti- vaccine. The salivary protein, PpSP15, was the first protective vaccine candidate against . Additionally, PsSP9 was already introduced as a highly immunogenic salivary protein against . Herein, we aimed to develop an effective multivalent live vaccine to control Cutaneous Leishmaniasis induced by two main species, and . Hence, the two above-mentioned salivary proteins using T2A linker were incorporated inside the genome as a safe live vector. Then, the immunogenicity and protective effects of recombinant co-expressing PpSP15 and PsSP9 were evaluated in pre-treated BALB/c mice with CpG against and . Following the cytokine assays, parasite burden and antibody assessment at different time-points at pre and post-infection, promising protective Th1 immunity was obtained in vaccinated mice with recombinant co-expressing PpSP15 and PsSP9. This is the first study demonstrating the potency of a safe live vaccine based on the combination of different salivary proteins against the infectious challenge with two different species of .

摘要

利什曼病是一种被忽视的媒介传播疾病,由寄生虫通过受感染的沙蝇叮咬传播。目前的治疗方法有限,部分原因是其成本高且副作用大,而且尚未有针对人类的疫苗。沙蝇唾液已被研究用于潜在的疫苗应用。唾液蛋白 PpSP15 是第一个针对 的保护性疫苗候选物。此外,PsSP9 已被引入作为一种针对 的高度免疫原性唾液蛋白。在此,我们旨在开发一种有效的多价活疫苗来控制由 和 两种主要物种引起的皮肤利什曼病。因此,使用 T2A 接头将上述两种唾液蛋白掺入 基因组内作为安全的活载体。然后,用 CpG 预处理 BALB/c 小鼠,评估重组 同时表达 PpSP15 和 PsSP9 的免疫原性和保护效果,以对抗 和 。在细胞因子分析后,在感染前和感染后不同时间点进行寄生虫负荷和抗体评估,在接种重组 同时表达 PpSP15 和 PsSP9 的小鼠中获得了有希望的保护性 Th1 免疫。这是第一项研究,证明了基于不同唾液蛋白组合的安全活疫苗针对两种不同物种的传染性挑战的效力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a33e/9226313/1660fb51805b/fimmu-13-895234-g001.jpg

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