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

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.

journal_name

J Virol

journal_title

Journal of virology

authors

Parker AL,Waddington SN,Buckley SM,Custers J,Havenga MJ,van Rooijen N,Goudsmit J,McVey JH,Nicklin SA,Baker AH

doi

10.1128/JVI.01878-08

subject

Has Abstract

pub_date

2009-01-01 00:00:00

pages

479-83

issue

1

eissn

0022-538X

issn

1098-5514

pii

JVI.01878-08

journal_volume

83

pub_type

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