Effect of Neutralizing Sera on Factor X-Mediated Adenovirus Serotype 5 Gene Transfer-Reference-Cited by-同舟云学术

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

Published:2009-01 Issue:1 Volume:83 Page:479-483
ISSN:0022-538X
Container-title:Journal of Virology
language:en
Short-container-title:J Virol

Author:

Parker Alan L.¹,Waddington Simon N.²,Buckley Suzanne M. K.²,Custers Jerome³,Havenga Menzo J. E.⁴,van Rooijen Nico⁵,Goudsmit Jaap³,McVey John H.⁶,Nicklin Stuart A.¹,Baker Andrew H.¹

Affiliation:

1. British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, United Kingdom

2. Department of Haematology, Haemophilia Centre and Thrombosis Unit, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, United Kingdom

3. Crucell Holland BV, P.O. Box 2048, 2301 CA Leiden, The Netherlands

4. TNO Biosciences, P.O. Box 2215, 2301CE Leiden, The Netherlands

5. Department of Molecular Cell Biology, Vrije Universiteit Medical Center (VUMC), 1081 BT Amsterdam, The Netherlands

6. Thrombosis Research Institute, Manresa Road, London SW3 6LR, United Kingdom

Abstract

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.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

Link

https://journals.asm.org/doi/pdf/10.1128/JVI.01878-08

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