Effect of Neutralizing Sera on Factor X-Mediated Adenovirus Serotype 5 Gene Transfer

A.J. Parker, S.N. Waddington, S.M.K. Buckley, J. Custers, M.J.E. Havenga, N. van Rooijen, J.F. Goudsmit, J.H. Mcvey, S.A. Nicklin, A.J.M. Baker

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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
Original languageUndefined/Unknown
Pages (from-to)479-483
JournalJournal of Virology
Volume83
Issue number1
DOIs
Publication statusPublished - 2009

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