Effect of neutralizing sera on factor X-mediated adenovirus serotype 5 gene transfer

Parker, A.L., Waddington, S.N., Buckley, S.M.K., Custers, J., Havenga, M.J.E., van Rooijen, N., Goudsmit, J., Mcvey, J.H., Nicklin, S.A. and Baker, A.H. (2009) Effect of neutralizing sera on factor X-mediated adenovirus serotype 5 gene transfer. Journal of Virology, 83(1), pp. 479-483. (doi: 10.1128/JVI.01878-08)

Abstract

The deployment of adenovirus serotype 5 (Ad5)-based vectors is hampered by preexisting immunity. When such vectors are delivered intravenously, hepatocyte transduction is mediated by the hexon-coagulation factor X (FX) interaction. Here, we demonstrate that human sera efficiently block FX-mediated cellular binding and transduction of Ad5-based vectors in vitro. Neutralizing activity correlated well with the ability to inhibit Ad5-mediated liver transduction, suggesting that prescreening patient sera in this manner accurately predicts the efficacy of Ad5-based gene therapies. Neutralization in vitro can be partially bypassed by pseudotyping with Ad45 fiber protein, indicating that a proportion of neutralizing antibodies are directed against the Ad5 fiber.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Nicklin, Professor Stuart and Baker, Professor Andrew and Parker, Dr Alan
• Authors: Parker, A.L., Waddington, S.N., Buckley, S.M.K., Custers, J., Havenga, M.J.E., van Rooijen, N., Goudsmit, J., Mcvey, J.H., Nicklin, S.A., and Baker, A.H.
• Subjects: Q Science > QH Natural history > QH345 Biochemistry
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Journal of Virology
• Journal Abbr.: J. Virol.
• Publisher: American Society for Microbiology
• ISSN: 0022-538X
• ISSN (Online): 1098-5514
• Published Online: 22 October 2008