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

Parker, AL, Waddington, SN, Buckley, SM, Custers, J, Havenga, MJ, van Rooijen, N, Goudsmit, J, McVey, JH, Nicklin, SA and Baker, AH (2009) Effect of neutralizing sera on factor x-mediated adenovirus serotype 5 gene transfer. J Virol, 83 (1). pp. 479-483.

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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.

Item Type:	Article
Authors :	Name Email ORCID Parker, AL Waddington, SN Buckley, SM Custers, J Havenga, MJ van Rooijen, N Goudsmit, J McVey, JH j.mcvey@surrey.ac.uk Nicklin, SA Baker, AH
Date :	January 2009
DOI :	10.1128/JVI.01878-08
Uncontrolled Keywords :	Adenoviridae, Cell Line, Tumor, Factor X, Genetic Therapy, Genetic Vectors, Hepatocytes, Humans, Immune Sera, Neutralization Tests, Transduction, Genetic, Virus Attachment
Related URLs :	Author
Depositing User :	Symplectic Elements
Date Deposited :	17 May 2017 09:56
Last Modified :	16 Jan 2019 17:51
URI:	http://epubs.surrey.ac.uk/id/eprint/825753

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