Laboratory of Antigen Targeting to Dendritic Cells, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, 05508-000, Brazil.
CTCMol, Federal University of São Paulo, São Paulo, 04044-010, Brazil.
Sci Rep. 2016 Dec 21;6:39250. doi: 10.1038/srep39250.
In vivo antigen targeting to dendritic cells (DCs) has been used as a way to improve immune responses. Targeting is accomplished with the use of monoclonal antibodies (mAbs) to receptors present on the DC surface fused with the antigen of interest. An anti-DEC205 mAb has been successfully used to target antigens to the DEC205CD8α DC subset. The administration of low doses of the hybrid mAb together with DC maturation stimuli is able to activate specific T cells and induce production of high antibody titres for a number of different antigens. However, it is still not known if this approach would work with any fused protein. Here we genetically fused the αDEC205 mAb with two fragments (42-kDa and 19-kDa) derived from the ~200 kDa Plasmodium vivax merozoite surface protein 1 (MSP1), known as MSP1 and MSP1, respectively. The administration of two doses of αDEC-MSP1, but not of αDEC-MSP1 mAb, together with an adjuvant to two mouse strains induced high anti-MSP1 antibody titres that were dependent on CD4 T cells elicited by peptides present in the MSP1 sequence, indicating that the presence of T cell epitopes in antigens targeted to DEC205 DCs increases antibody responses.
体内抗原靶向树突状细胞 (DC) 已被用作提高免疫反应的一种方法。通过使用与感兴趣的抗原融合的存在于 DC 表面上的受体的单克隆抗体 (mAb) 来实现靶向。抗 DEC205 mAb 已成功用于将抗原靶向 DEC205CD8α DC 亚群。低剂量的杂交 mAb 与 DC 成熟刺激物一起给药能够激活特异性 T 细胞，并诱导针对许多不同抗原的高抗体滴度的产生。然而，目前尚不清楚这种方法是否适用于任何融合蛋白。在这里，我们将 αDEC205 mAb 与源自约 200 kDa 间日疟原虫裂殖子表面蛋白 1 (MSP1) 的两个片段（42 kDa 和 19 kDa）基因融合，分别称为 MSP1 和 MSP1。两剂量的 αDEC-MSP1，而不是 αDEC-MSP1 mAb，与佐剂一起给药给两种小鼠品系，诱导了高抗 MSP1 抗体滴度，这取决于 MSP1 序列中存在的肽诱导的 CD4 T 细胞，表明靶向 DEC205 DC 的抗原中 T 细胞表位的存在增加了抗体反应。
