Antigen Targeting to Human HLA Class II Molecules Increases Efficacy of DNA Vaccination
Antigen Targeting to Human HLA Class II Molecules Increases Efficacy of DNA Vaccination
复制标题
DOI：
10.4049/jimmunol.1600893
复制
发表时间：
2016-11-01
影响因子：
4.4
通讯作者：
Bogen, Bjarne
中科院分区：
文献类型：
--
作者：
Grodeland, Gunnveig;Fredriksen, Agnete Brunsvik;Bogen, Bjarne
很难将小鼠 DNA 疫苗接种的有希望的结果转化为更大的动物和人类。此前，编码将 Ag 靶向 APC 上的 MHC II 类 (MHC-II) 分子的蛋白质的 DNA 疫苗已被证明可以在小鼠体内诱导快速、增强且持久的 Ag 特异性抗体滴度。在这项研究中，我们描述了两种新型 DNA 疫苗，它们作为靶向 HLA II 类 (HLA-II) 分子的蛋白质。这些疫苗蛋白与多种大型哺乳动物的 MHC-II 分子发生交叉反应。在雪貂和猪中进行测试时，使用低剂量 HLA-II 靶向疫苗进行单次 DNA 递送可导致快速且增强的抗体反应。重要的是，无痛皮内喷射递送 DNA 与针头注射然后电穿孔递送一样有效。表明这些疫苗也可用于人类，我们发现 HLA-II 靶向疫苗蛋白在体外可将人类 CD4(+) T 细胞反应提高 10(3) 倍。因此，将 Ag 靶向 MHC-II 分子可能是提高 DNA 疫苗在大型动物和人类中的功效的一种有吸引力的策略。
It has been difficult to translate promising results from DNA vaccination in mice to larger animals and humans. Previously, DNA vaccines encoding proteins that target Ag to MHC class II (MHC-II) molecules on APCs have been shown to induce rapid, enhanced, and long-lasting Ag-specific Ab titers in mice. In this study, we describe two novel DNA vaccines that as proteins target HLA class II (HLA-II) molecules. These vaccine proteins cross-react with MHC-II molecules in several species of larger mammals. When tested in ferrets and pigs, a single DNA delivery with low doses of the HLA-II targeted vaccines resulted in rapid and increased Ab responses. Importantly, painless intradermal jet delivery of DNA was as effective as delivery by needle injection followed by electroporation. As an indication that the vaccines could also be useful for human application, HLA-II targeted vaccine proteins were found to increase human CD4(+) T cell responses by a factor of x 10(3) in vitro. Thus, targeting of Ag to MHC-II molecules may represent an attractive strategy for increasing efficacy of DNA vaccines in larger animals and humans.