Porcine adenoviral vectors evade preexisting humoral immunity to adenoviruses and efficiently infect both human and murine cells in culture.
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.
Bangari
Dinesh S
DS
Laboratory of Gene Therapy and Purdue University Cancer Center, 1290 Lynn Hall, Purdue University, West Lafayette, IN 47907, USA.
Mittal
Suresh K
SK
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
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