title: Porcine adenoviral vectors evade preexisting humoral immunity to adenoviruses and efficiently infect both human and murine cells in culture.
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 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.
authors.affiliation: Laboratory of Gene Therapy and Purdue University Cancer Center, 1290 Lynn Hall, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Dinesh S
authors.initials: DS
authors.lastname: Bangari
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Mittal
mesh_terms: D017500:Adenovirus E1A Proteins / Q000235:genetics; D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D025662:Adenoviruses, Porcine / Q000235:genetics* / Q000276:immunology* / Q000502:physiology; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D002460:Cell Line; D045744:Cell Line, Tumor; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D003429:Cross Reactions; D017353:Gene Deletion; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D009500:Neutralization Tests; D011991:Receptors, Virus / Q000378:metabolism; D014161:Transduction, Genetic; D014779:Virus Replication
chemical_list: D017500:Adenovirus E1A Proteins; D000914:Antibodies, Viral; C568771:CLMP protein, human; C568772:CLMP protein, mouse; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D011991:Receptors, Virus; D049452:Green Fluorescent Proteins