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Title: Neutralizing antibodies against adeno-associated virus examined prospectively in pediatric patients with hemophilia
Authors: C. Li
N. Narkbunnam
R. J. Samulski
A. Asokan
G. Hu
L. J. Jacobson
M. J. Manco-Johnson
P. E. Monahan
Marilyn J. Manco-Johnson
Brenda Riske
Ray Kilcoyne
Michael L. Manco-Johnson
Sharon Funk
Linda Jacobson
J. David Ingram
Thomas C. Abshire
Amy D. Shapiro
Michele R. Hacker
Leonard A. Valentino
W. Keith Hoots
Deborah Brown
George R. Buchanan
Donna DiMichele
Michael Recht
Cindy Leissinger
Shirley Bleak
Alan Cohen
Prasad Mathew
Alison Matsunaga
Desiree Medeiros
Diane Nugent
Gregory A. Thomas
Alexis A. Thompson
Kevin McRedmond
J. Michael Soucie
Harlan Austin
Bruce L. Evatt
The University of North Carolina at Chapel Hill
Mahidol University
University of Colorado School of Medicine
University of Colorado Health Sciences Center
Emory University
Blood Center of Milwaukee
Indiana Hemophilia and Thrombosis Center
Harvard Medical School
Rush University Medical Center
University of Texas System
University of Southwestern Medical Center
Weill Cornell Medical College
Phoenix Children's Hospital
Tulane University
Primary Children's Medical Center
University of Pennsylvania
University of New Mexico
UCSF Benioff Children's Hospital Oakland
University of Hawaii at Manoa
CHOC Children`s UC Irvine School of Medicine
Oregon Health and Science University
Northwestern University
Palmetto Health Richland
Centers for Disease Control and Prevention
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Mar-2012
Citation: Gene Therapy. Vol.19, No.3 (2012), 288-294
Abstract: Recombinant adeno-associated virus (rAAV) is a promising gene delivery vector and has recently been used in patients with hemophilia. One limitation of AAV application is that most humans have experienced wild-type AAV serotype 2 exposure, which frequently generates neutralizing antibodies (NAbs) that may inhibit rAAV2 vector transduction. Employing alternative serotypes of rAAV vectors may circumvent this problem. We investigated the development of NAbs in early childhood by examining sera gathered prospectively from 62 children with hemophilia A, participating in a multi-institutional hemophilia clinical trial (the Joint Outcome Study). Clinical applications in hemophilia therapy have been suggested for serotypes AAV2, AAV5 and AAV8, therefore NAbs against these serotypes were serially assayed over a median follow-up of 4 years. NAbs prevalence increased during early childhood for all serotypes. NAbs against AAV2 (43.5%) were observed more frequently and at higher titers compared with both AAV5 (25.8%) and AAV8 (22.6%). NAbs against AAV5 or AAV8 were rarely observed in the absence of co-prevalent and higher titer AAV2 NAbs, suggesting that NAbs to AAV5 and AAV8 were detected following AAV2 exposure due to partial cross-reactivity of AAV2-directed NAbs. The results may guide rational design of clinical trials using alternative AAV serotypes and suggest that younger patients who are given AAV gene therapy will benefit from the lower prevalence of NAbs. © 2012 Macmillan Publishers Limited All rights reserved.
ISSN: 14765462
Appears in Collections:Scopus 2011-2015

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