Laboratory of Synthetic Protein Chemistry, The Rockefeller University, New York, New York, USA.
Nat Chem Biol. 2013 Apr;9(4):250-6. doi: 10.1038/nchembio.1186. Epub 2013 Feb 17.
Targeted delivery of antigens to dendritic cells (DCs) is a promising vaccination strategy. However, to ensure immunity, the approach depends on coadministration of an adjuvant. Here we ask whether targeting of both adjuvant and antigen to DCs is sufficient to induce immunity. Using a protein ligation method, we develop a general approach for linking the immune stimulant, poly dA:dT (pdA:dT), to a monoclonal antibody (mAb) specific for DEC205 (DEC). We show that DEC-specific mAbs deliver pdA:dT to DCs for the efficient production of type I interferon in human monocyte-derived DCs and in mice. Notably, adaptive T-cell immunity is elicited when mAbs specific for DEC-pdA:dT are used as the activation stimuli and are administered together with a DC-targeted antigen. Collectively, our studies indicate that DCs can integrate innate and adaptive immunity in vivo and suggest that dual delivery of antigen and adjuvant to DCs might be an efficient approach to vaccine development.
将抗原靶向递送至树突状细胞 (DC) 是一种很有前途的疫苗接种策略。然而，为了确保免疫，该方法取决于佐剂的共同给药。在这里，我们想知道将佐剂和抗原都靶向 DC 是否足以诱导免疫。我们使用蛋白连接方法，开发了一种将免疫刺激剂聚脱氧腺苷: 脱氧胸苷 (pdA:dT) 连接到针对 DEC205 (DEC) 的单克隆抗体 (mAb) 的通用方法。我们表明，针对 DEC 的 mAb 将 pdA:dT 递送至 DC，从而在人单核细胞衍生的 DC 中和在小鼠中有效地产生 I 型干扰素。值得注意的是，当使用针对 DEC-pdA:dT 的 mAb 作为激活刺激物并与靶向 DC 的抗原一起给药时，会引发适应性 T 细胞免疫。总的来说，我们的研究表明 DC 可以在体内整合先天免疫和适应性免疫，并表明将抗原和佐剂双重递送至 DC 可能是一种有效的疫苗开发方法。
