Immunogenicity of DNA vaccines can be increased by constructing the DNA in such a way that it encodes secreted homodimeric fusion proteins that target antigen-presenting cells (APCs). In this study, we have developed novel APC-targeting vaccine molecules with an increased flexibility due to introduction of a heterodimerization motif. The heterodimeric proteins permit four different fusions within a single molecule, thus allowing expression of two different APC-targeting moieties and two different antigens. Two types of heterodimeric fusion proteins were developed that employed either the ACID/BASE or the Barnase/Barstar motifs, respectively. The ACID/BASE heterodimeric vaccines conferred protection against challenges with either influenza virus or tumor cells in separate preclinical models. The ACID/BASE motif was flexible since a large number of different targeting moieties and antigens could be introduced with maintenance of specificity, antigenicity, and secretion. APC-targeting ACID/BASE vaccines expressing two different antigens induced antibody and T cell responses against either of the two antigens. Heterodimeric ACID/BASE DNA vaccines were of approximately the same potency as previously reported homodimeric DNA vaccines. The flexibility and potency of the ACID/BASE format suggest that it could be a useful platform for DNA vaccines that encode APC-targeting fusion proteins.

中文翻译：

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编码抗原呈递细胞的异二聚体蛋白的DNA疫苗可预防癌症和流行性感冒。

DNA疫苗的免疫原性可以通过构建DNA来提高，从而使其编码靶向抗原呈递细胞（APC）的分泌的同型二聚体融合蛋白。在这项研究中，我们开发了新型的针对APC的疫苗分子，由于引入了异二聚体基序，具有更高的灵活性。异二聚体蛋白允许在单个分子内进行四种不同的融合，从而允许表达两种不同的靶向APC的部分和两种不同的抗原。已开发出两种类型的异二聚体融合蛋白，分别使用ACID / BASE或Barnase / Barstar基序。ACID / BASE异二聚体疫苗可在单独的临床前模型中提供针对流感病毒或肿瘤细胞攻击的保护作用。ACID / BASE基序是灵活的，因为可以引入许多不同的靶向部分和抗原以维持特异性，抗原性和分泌。表达两种不同抗原的靶向APC的ACID / BASE疫苗可诱导针对两种抗原中任一种的抗体和T细胞应答。异二聚体ACID / BASE DNA疫苗的效力与以前报道的同二聚体DNA疫苗大致相同。ACID / BASE格式的灵活性和效力表明，它可能是编码靶向APC的融合蛋白的DNA疫苗的有用平台。表达两种不同抗原的靶向APC的ACID / BASE疫苗可诱导针对两种抗原中任一种的抗体和T细胞应答。异二聚体ACID / BASE DNA疫苗的效力与以前报道的同二聚体DNA疫苗大致相同。ACID / BASE格式的灵活性和效力表明，它可能是编码靶向APC的融合蛋白的DNA疫苗的有用平台。表达两种不同抗原的靶向APC的ACID / BASE疫苗可诱导针对两种抗原中任一种的抗体和T细胞应答。异二聚体ACID / BASE DNA疫苗的效力与以前报道的同二聚体DNA疫苗大致相同。ACID / BASE格式的灵活性和效力表明，它可能是编码靶向APC的融合蛋白的DNA疫苗的有用平台。