Adjuvanted multi-epitope vaccines protect HLA-A*11:01 transgenic mice against Toxoplasma gondii
Adjuvanted multi-epitope vaccines protect HLA-A*11:01 transgenic mice against Toxoplasma gondii
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DOI：
10.1172/jci.insight.85955
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发表时间：
2016-09-22
期刊：
影响因子：
8
通讯作者：
McLeod, Rima
中科院分区：
文献类型：
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作者：
El Bissati, Kamal;Chentoufi, Aziz A.;McLeod, Rima
我们使用 TLR4 配体乳剂佐剂（稳定乳剂中的葡萄糖吡喃葡萄糖脂质佐剂 [GLA-SE]）创建并测试了多表位 DNA 或蛋白质疫苗，以了解其在 HLA 转基因小鼠中预防弓形虫的能力。我们的构建体分别包含 5 个最佳下调的 CD8(+) T 细胞诱导表位、通用 CD4(+) 辅助 T 淋巴细胞表位 (PADRE) 和分泌信号，所有这些都旨在实现最佳的 MHC-I 呈现。通过对 HLA-A*11:01 转基因小鼠进行免疫，研究了它们引发免疫和保护性反应的能力。这些多表位疫苗增加了产生 IFN-γ 的记忆 CD8(+) T 细胞，并在受到弓形虫攻击时保护小鼠免受寄生虫负担。乳液捕获蛋白的内吞作用和抗原的交叉呈递必须解释我们的佐剂蛋白的免疫原性。因此，我们的工作创建了一个肽的佐剂平台组装，导致在预防弓形虫病的疫苗中交叉呈递 CD8(+) T 细胞诱导表位。
We created and tested multi-epitope DNA or protein vaccines with TLR4 ligand emulsion adjuvant (gluco glucopyranosyl lipid adjuvant in a stable emulsion [GLA-SE]) for their ability to protect against Toxoplasma gondii in HLA transgenic mice. Our constructs each included 5 of our best down-selected CD8(+) T cell-eliciting epitopes, a universal CD4(+) helper T lymphocyte epitope (PADRE), and a secretory signal, all arranged for optimal MHC-I presentation. Their capacity to elicit immune and protective responses was studied using immunization of HLA-A*11:01 transgenic mice. These multi-epitope vaccines increased memory CD8(+) T cells that produced IFN-gamma and protected mice against parasite burden when challenged with T. gondii. Endocytosis of emulsion-trapped protein and cross presentation of the antigens must account for the immunogenicity of our adjuvanted protein. Thus, our work creates an adjuvanted platform assembly of peptides resulting in cross presentation of CD8(+) T cell-eliciting epitopes in a vaccine that prevents toxoplasmosis.