457. Fibronectin Peptide Reduces the Immune Response to Adenovirus and Enhances Transgene Expression

Abstract

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 following 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. To compare transduction efficiencies of PAd3 and human adenovirus type 5 (HAd5) vectors, PAd-GFP (E1A-deleted PAd3 vector expressing green fluorescent protein; GFP) and HAd-GFP (E1-deleted HAd5 vector expressing GFP) were generated. PAd-GFP and HAd-GFP transduced human cell lines with comparable efficiencies. Both 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 vector system would be a promising supplement to HAd vectors as a delivery vehicle for recombinant vaccines and gene therapy applications.