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)
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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 |
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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 |
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