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评估在 BALB/c 模型中,经异源疫苗接种方案接种后,体外成熟的 BMDCs 呈递 CD8 T 细胞刺激肽诱导的保护作用。

Evaluation of protection induced by in vitro maturated BMDCs presenting CD8 T cell stimulating peptides after a heterologous vaccination regimen in BALB/c model against Leishmania major.

机构信息

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

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

出版信息

Exp Parasitol. 2021 Apr;223:108082. doi: 10.1016/j.exppara.2021.108082. Epub 2021 Feb 11.

Abstract

Leishmaniasis is a complex vector-borne disease mediated by Leishmania parasite and a strong and long-lasting CD4 Th1 and CD8-T cell immunity is required to control the infection. Thus far multivalent subunit vaccines have met this requirement more promisingly. However several full protein sequences cannot be easily arranged in one construct. Instead, new emerging immune-informatics based epitope formulations surpass this restriction. Herein, we aimed to examine the protective potential of a dendritic cell based vaccine presenting epitopes to CD8 and CD4-T cells in combination with DNA vaccine encoding the same epitopes against murine cutaneous leishmaniasis. Immature DCs were loaded with epitopes (selected from parasite proteome) in vitro with or without CpG oligonucleotides and were used to immunize BALB/c mice. Peptide coding DNA was used to boost the system and immunological responses were evaluated after Leishmania (L.) major infectious challenge. The pre-challenge response to included epitopes was Th1 polarized which potentially lowered the infection at early time points post-challenge but not at later weeks. Collectively, DC prime-DNA boost was found to be a promising approach for Th1 polarization however the constituent epitopes undoubtedly make a significant contribution in the protection outcome of the vaccine.

摘要

利什曼病是一种由利什曼原虫介导的复杂的媒介传播疾病,需要强烈和持久的 CD4 Th1 和 CD8-T 细胞免疫来控制感染。到目前为止,多价亚单位疫苗更有希望满足这一要求。然而,一些完整的蛋白质序列不容易在一个构建体中排列。相反,新出现的基于免疫信息学的表位配方克服了这一限制。在此,我们旨在研究树突状细胞疫苗在与编码相同表位的 DNA 疫苗联合使用时,向 CD8 和 CD4-T 细胞呈递表位的保护性潜力,以对抗小鼠皮肤利什曼病。未成熟的 DC 体外加载表位(从寄生虫蛋白质组中选择),或加载表位与 CpG 寡核苷酸联合使用,并用于免疫 BALB/c 小鼠。肽编码 DNA 用于增强系统,在利什曼(L.)主要感染挑战后评估免疫反应。包括表位的预挑战反应呈 Th1 极化,这可能会降低感染的风险,但在感染后几周内不会。总的来说,DC 疫苗接种-DNA 疫苗接种被认为是 Th1 极化的一种有前途的方法,然而,组成的表位无疑对疫苗的保护效果有显著的贡献。

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