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Journal of Virology, January 2009, p. 479-483, Vol. 83, No. 1
0022-538X/09/$08.00+0     doi:10.1128/JVI.01878-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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

Alan L. Parker,1 Simon N. Waddington,2 Suzanne M. K. Buckley,2 Jerome Custers,3 Menzo J. E. Havenga,4 Nico van Rooijen,5 Jaap Goudsmit,3 John H. McVey,6 Stuart A. Nicklin,1 and Andrew H. Baker1*

British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, United Kingdom,1 Department of Haematology, Haemophilia Centre and Thrombosis Unit, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, United Kingdom,2 Crucell Holland BV, P.O. Box 2048, 2301 CA Leiden, The Netherlands,3 TNO Biosciences, P.O. Box 2215, 2301CE Leiden, The Netherlands,4 Department of Molecular Cell Biology, Vrije Universiteit Medical Center (VUMC), 1081 BT Amsterdam, The Netherlands,5 Thrombosis Research Institute, Manresa Road, London SW3 6LR, United Kingdom6

Received 7 September 2008/ Accepted 10 October 2008

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.

* Corresponding author. Mailing address: British Heart Foundation Glasgow Cardiovascular Research Centre, Division of Cardiovascular and Medical Sciences, 126 University Place, University of Glasgow, Glasgow G12 8TA, United Kingdom. Phone: 44 141 330 1977. Fax: 44 141 330 6997. E-mail: ab11f{at}clinmed.gla.ac.uk

{triangledown} Published ahead of print on 22 October 2008.

Journal of Virology, January 2009, p. 479-483, Vol. 83, No. 1
0022-538X/09/$08.00+0     doi:10.1128/JVI.01878-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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