Bangari Dinesh S, Mittal Suresh K
Laboratory of Gene Therapy and Purdue University Cancer Center, 1290 Lynn Hall, Purdue University, West Lafayette, IN 47907, USA.
Virus Res. 2004 Oct;105(2):127-36. doi: 10.1016/j.virusres.2004.05.003.
Preexisting immunity against human adenoviruses (HAd) limits the efficiency of transduction of HAd vectors in humans. In addition, development of a vector-specific immune response after the first inoculation with a HAd vector further lowers vector uptake following readministration. We investigated the usefulness of porcine adenovirus serotype 3 (PAd3)-based vectors as a supplement to HAd vectors. Here we demonstrate that preexisting HAd-specific neutralizing antibodies in humans do not cross-neutralize PAd3. In order to generate E1A-deleted PAd3 vectors, an E1-complementing cell line of porcine origin was produced. E1A-deleted PAd3 vector expressing green fluorescent protein; GFP (PAd-GFP) and E1-deleted HAd5 vector expressing GFP (HAd-GFP) transduced human cell lines with comparable efficiencies. Both of these vectors efficiently transduced murine MT1A2 breast cancer cell line, while PAd-GFP transduced murine NIH 3T3 fibroblast cell line significantly better (P < 0.05) than HAd-GFP. These results suggest that PAd3 vectors would be promising supplement to HAd vectors as a delivery vehicle for recombinant vaccines and gene therapy applications.
针对人腺病毒(HAd)的既有免疫力会限制HAd载体在人体中的转导效率。此外,首次接种HAd载体后产生的载体特异性免疫反应会进一步降低再次给药后的载体摄取量。我们研究了基于猪腺病毒3型(PAd3)的载体作为HAd载体补充物的效用。在此我们证明,人体中预先存在的HAd特异性中和抗体不会交叉中和PAd3。为了构建缺失E1A的PAd3载体,制备了一种猪源的E1互补细胞系。表达绿色荧光蛋白(GFP)的缺失E1A的PAd3载体(PAd-GFP)和表达GFP的缺失E1的HAd5载体(HAd-GFP)以相当的效率转导人细胞系。这两种载体都能高效转导鼠MT1A2乳腺癌细胞系,而PAd-GFP转导鼠NIH 3T3成纤维细胞系的效果明显优于HAd-GFP(P < 0.05)。这些结果表明,作为重组疫苗和基因治疗应用的递送载体,PAd3载体有望成为HAd载体的补充物。