Genethon, 91002, Evry cedex, France.
INSERM U1151, Institut Necker Enfants Malades, CNRS, Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, UMR8253, Paris, France.
Sci Rep. 2019 Mar 8;9(1):3937. doi: 10.1038/s41598-019-40594-7.
The discovery of tumor-associated antigens recognized by T lymphocytes opens the possibility of vaccinating cancer patients with defined antigens. However, one of the major limitation of peptide-based vaccines is the low immunogenicity of antigenic peptides. Interestingly, if these epitopes are directly delivered into the cytoplasm of antigen presenting cells, they can be efficiently presented via the direct MHC class I presentation pathway. To improve antigen entry, one promising approach is the use of cell penetrating peptides (CPPs). However, most studies use a covalent binding of the CPP with the antigen. In the present study, we focused on the C-terminal domain of Vpr which was previously demonstrated to efficiently deliver plasmid DNA into cells. We provide evidence that the peptides Vpr55-91 and Vpr55-82 possess the capacity of delivering proteins and epitopes into cell lines as well as into human primary dendritic cells, without the necessicity for a chemical linkage. Moreover, immunization of HLA-A2 transgenic mice with Vpr55-91 as the sole adjuvant is able to induce antigen-specific cytotoxic T lymphocytes against multiple tumor epitopes.
肿瘤相关抗原被 T 淋巴细胞识别的发现为癌症患者接种特定抗原疫苗开辟了可能性。然而，基于肽的疫苗的主要局限性之一是抗原肽的免疫原性低。有趣的是，如果这些表位直接递送到抗原呈递细胞的细胞质中，它们可以通过直接 MHC 类 I 呈递途径有效地呈递。为了提高抗原的进入，一种很有前途的方法是使用细胞穿透肽 (CPP)。然而，大多数研究使用 CPP 与抗原的共价结合。在本研究中，我们专注于 Vpr 的 C 末端结构域，先前的研究表明它可以有效地将质粒 DNA 递送到细胞中。我们提供的证据表明，肽 Vpr55-91 和 Vpr55-82 具有将蛋白质和表位递送到细胞系以及人类原代树突状细胞的能力，而不需要化学连接。此外，用 Vpr55-91 作为唯一佐剂对 HLA-A2 转基因小鼠进行免疫接种，能够诱导针对多种肿瘤表位的抗原特异性细胞毒性 T 淋巴细胞。
