ppat.1007395.g002.tif (563.84 kB)
Impact of anti-vector immunity on transgene expression.
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posted on 2018-12-05, 19:08 authored by Hugh C. Welles, Madeleine F. Jennewein, Rosemarie D. Mason, Sandeep Narpala, Lingshu Wang, Cheng Cheng, Yi Zhang, John-Paul Todd, Jeffrey D. Lifson, Alejandro B. Balazs, Galit Alter, Adrian B. McDermott, John R. Mascola, Mario Roederer(A) Anti-vector reactivity and (B) expression of ITS01 is shown for the six animals of Fig 1. Animals with low (A10V030; orange) and intermediate (A10V026; purple) pre-existing anti-vector immunity are highlighted. After 6 months, two of these animals were re-injected with 1 x 1013 gc AAV8-ITS01 in the right quadriceps. (C) Anti-AAV8 reactivity was boosted, however (D) no increase in serum ITS01 was observed. Anti-AAV8 measurements are in arbitrary optical density (OD450nm)/ml units.
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AAV-directed muscle cell expressionanti-transgene antibody responsetarget antibody abundanceAAV-based approachesVectored deliveryautologous anti-SIV neutralizing antibodiesimmunization strategyanimal modelVectored transgene expressionplasma expressionmucosal accumulationtransgene mAbdose SIVsmE 660 swarm challengedose intrarectal swarm SIVsmE 660 challenge Geneinjectionglycosylation profilesanti-SIV envelopeanti-vector antibody responsesAAV 8nonhuman primate modelAdeno-Associated Virus 8HIVgene therapy-basedimmunity2 x 10 12 AAV 8 genome copiesmucosal surfacesrhesus macaques
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