ppat.1007395.g001.tif (570.05 kB)
Stable transgene mAb expression following AAV8 administration in NHP.
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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 RoedererRhesus macaques were injected with both AAV8-ITS01 and AAV8-ITS06.02 at 1 x 1013 gc/mAb/animal in the right and left quadriceps, respectively. (A) Serum ITS01 (blue lines) and ITS06.02 (red lines) and their sum (black lines) are shown individually for each animal over time following injection. (B) The average and standard deviation of expression levels are shown across all animals. Dashed lines indicate the lower limit of detection by binding to SIVmac239 gp140 (2 standard deviations above negative control sera) for ITS01 (blue), ITS06.02 (red). Asterisks denote statistically significant difference between mean ITS01 and ITS06.02 expression at week 4 (p ≤ 0.05).
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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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