Fotoran Wesley L, Santangelo Rachele, de Miranda Beatriz N M, Irvine Darrell J, Wunderlich Gerhard
Department of Parasitology, Institute for Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1374, São Paulo, 05508000, Brazil.
Institute of Chemistry of São Carlos, University of São Paulo, Av. Trabalhador São-Carlense 400, São Carlos, 13566-590, Brazil.
Mol Ther Methods Clin Dev. 2017 Aug 23;7:1-10. doi: 10.1016/j.omtm.2017.08.004. eCollection 2017 Dec 15.
The delivery of antigens as DNA vaccines is an efficient alternative to induce immune responses against antigens, which are difficult to produce in recombinant form. However, the delivery of naked DNA is ineffective or relies on sophisticated ballistic devices. Here, we show a combination of liposome application and naked DNA vaccine that successfully overcomes these problems. Upon entrapment of plasmids encoding different antigens in cationic particles, transfection efficiencies similar to commercial kits were achieved in in vitro cell cultures. The liposome-based approach provided strong humoral responses against three malarial antigens, namely the Circumsporozoite protein and the C terminus of merozoite surface protein 1 from (titers 10 or 10-10, respectively) and Rhoptry antigen 5 from (titers 10-10). When employed in growth-inhibition assays, antibodies demonstrated consistent reinvasion-blocking activities that were dose dependent. Liposome-formulated DNA vaccines may prove useful when targets cannot be produced as recombinant proteins and when conformation-dependent and highly specific antibodies are mandatory.
作为DNA疫苗的抗原递送是诱导针对难以以重组形式生产的抗原产生免疫反应的有效替代方法。然而，裸DNA递送无效或依赖于复杂的弹道装置。在这里，我们展示了脂质体应用与裸DNA疫苗的组合，成功克服了这些问题。当将编码不同抗原的质粒包裹在阳离子颗粒中时，在体外细胞培养中实现了与商业试剂盒相似的转染效率。基于脂质体的方法针对三种疟疾抗原产生了强烈的体液反应，即环子孢子蛋白和来自疟原虫的裂殖子表面蛋白1的C末端（效价分别为10或10-10）以及来自疟原虫的棒状体抗原5（效价为10-10）。当用于生长抑制试验时，抗体表现出一致的剂量依赖性再侵入阻断活性。当靶标不能作为重组蛋白生产且需要构象依赖性和高度特异性抗体时，脂质体制备的DNA疫苗可能会被证明是有用的。
