Influenza Research Laboratory, Pasteur Institute of Iran, Tehran, Iran.
Immunol Lett. 2012 Nov-Dec;148(1):77-82. doi: 10.1016/j.imlet.2012.08.006. Epub 2012 Sep 7.
DNA vaccines have emerged as an attractive approach to induce CTL responses against cancer and infectious agents in recent years. Although CTL induction by DNA vaccination would be a valuable strategy for controlling viral infections, increasing the potency of DNA vaccines is mandatory before DNA vaccines can make it to the clinic. In this study, we developed and characterized a new and safe adjuvanted delivery system for DNA vaccination using cationic influenza virosomes (CIV). CIV were produced by reconstitution of detergent-solubilized influenza virus membranes in the presence of cationic lipids. Plasmid DNA (pDNA) mixed with these virosomes was efficiently transfected into cells of a mouse macrophage cell line (RAW-Blue cells). Moreover, the cells were effectively activated as demonstrated by production of an NFκB/AP-1-inducible reporter enzyme. Following three intradermal immunizations, CIV-delivered epitope-encoding pDNA induced equal numbers of IFNγ- and granzyme B-producing T cells than a 10-fold higher dose of naked pDNA. Virosomes without cationic lipids also improved induction of cellular immunity by pDNA but to a significantly lower extent than CIV. These findings suggest that pDNA-CIV complexes could be an efficacious delivery system suitable for CTL induction by DNA vaccination.
近年来，DNA 疫苗作为一种有吸引力的方法，在诱导针对癌症和传染性病原体的 CTL 反应方面取得了进展。虽然 DNA 疫苗诱导 CTL 反应将是控制病毒感染的一种有价值的策略，但在 DNA 疫苗进入临床应用之前，提高 DNA 疫苗的效力是强制性的。在这项研究中，我们开发并表征了一种新的安全的 DNA 疫苗佐剂传递系统，使用阳离子流感病毒囊泡（CIV）。CIV 是通过在阳离子脂质存在下，将去污剂溶解的流感病毒膜重新组装而产生的。与这些病毒囊泡混合的质粒 DNA（pDNA）有效地转染到一种小鼠巨噬细胞系（RAW-Blue 细胞）的细胞中。此外，细胞被有效地激活，如 NFκB/AP-1 诱导的报告酶的产生所证明。经过三次皮内免疫，CIV 递送的表位编码 pDNA 诱导的 IFNγ-和颗粒酶 B 产生的 T 细胞数量与 10 倍更高剂量的裸 pDNA 相当。没有阳离子脂质的病毒囊泡也能改善 pDNA 诱导的细胞免疫，但程度明显低于 CIV。这些发现表明，pDNA-CIV 复合物可能是一种有效的 DNA 疫苗诱导 CTL 反应的递送系统。
