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

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Parker, A.L.

Waddington, S.N.

Buckley, S.M.K.

Custers, J.

Havenga, M.J.E.

Rooijen, N. van

Goudsmit, J.

McVey, J.H.

Nicklin, S.A.

Baker, A.H.
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. Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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Biomedical ResearchAdenovirusCorrelation analysisFiberGene therapyGene transferGenetic transductionImmunityIn vitro studyLiver cellNonhumanPriority journalPseudotypingScreeningSerotypeGene vectorHumanImmunologyMetabolismMethodologySerodiagnosisTumor cell lineVirologyVirus attachmentAdenoviridaeantiserumblood clotting factor 10AdenoviridaeCell Line, TumorFactor XGene TherapyGenetic VectorsHepatocytesHumansImmune SeraNeutralization TestsTransduction, GeneticVirus Attachment
TNO Identifier
285077
Repository link
https://resolver.tno.nl/uuid:2414e48c-c404-4661-a153-171365b4391c
Source
Journal of Virology, 83(Jan), pp. 479-483.
Pages
479-483
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