Department of Opthalmology and Visual Science; and Department of Pediatrics, Infectious Diseases Division (RM), The University of Chicago, Chicago, Illinois, USA.
Pathology and Clinical Laboratory Medicine, Department of Immunology, King Fahad Medical City, Riyadh, Saudi Arabia.
JCI Insight. 2016 Sep 22;1(15):e85955. doi: 10.1172/jci.insight.85955.
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 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-γ and protected mice against parasite burden when challenged with . . 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.
我们构建并测试了含有 TLR4 配体乳剂佐剂(稳定乳剂中的葡萄糖-葡糖苷基脂质佐剂[GLA-SE])的多表位 DNA 或蛋白疫苗,以评估其在 HLA 转基因小鼠中的保护作用。我们的构建体每个都包含了我们最好的 5 个被选择的 CD8 T 细胞激发表位、一个通用的 CD4 辅助 T 淋巴细胞表位(PADRE)和一个分泌信号,所有这些都是为了优化 MHC-I 呈递而排列的。通过 HLA-A*11:01 转基因小鼠的免疫接种研究了它们引发免疫和保护反应的能力。这些多表位疫苗增加了产生 IFN-γ 的记忆 CD8 T 细胞,并在受到弓形虫挑战时保护小鼠免受寄生虫负担。乳剂捕获的蛋白质的内吞作用和抗原的交叉呈递必须解释我们佐剂化蛋白的免疫原性。因此,我们的工作创建了一个经过修饰的肽平台,在疫苗中交叉呈递 CD8 T 细胞激发表位,从而预防弓形体病。