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J Virol. 2009 Jan;83(1):479-83. doi: 10.1128/JVI.01878-08. Epub 2008 Oct 22.

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

Author information

1
British Heart Foundation Glasgow Cardiovascular Research Centre, Division of Cardiovascular and Medical Sciences, 126 University Place, University of Glasgow, Glasgow G12 8TA, United Kingdom. ab11f@clinmed.gla.ac.uk

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.

PMID:
18945780
PMCID:
PMC2612319
DOI:
10.1128/JVI.01878-08
[Indexed for MEDLINE]
Free PMC Article

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