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

Alan L Parker, Simon N Waddington, Suzanne M K Buckley, Jerome Custers, Menzo J E Havenga, Nico van Rooijen, Jaap Goudsmit, John H McVey, Stuart A Nicklin, Andrew H Baker

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)479-83
Number of pages5
JournalJournal of Virology
Volume83
Issue number1
DOIs
Publication statusPublished - Jan 2009

Keywords

  • Adenoviridae
  • Cell Line, Tumor
  • Factor X
  • Genetic Therapy
  • Genetic Vectors
  • Hepatocytes
  • Humans
  • Immune Sera
  • Neutralization Tests
  • Transduction, Genetic
  • Virus Attachment

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