C. LiN. NarkbunnamR. J. SamulskiA. AsokanG. HuL. J. JacobsonM. J. Manco-JohnsonP. E. MonahanMarilyn J. Manco-JohnsonBrenda RiskeRay KilcoyneMichael L. Manco-JohnsonSharon FunkLinda JacobsonJ. David IngramThomas C. AbshireAmy D. ShapiroMichele R. HackerLeonard A. ValentinoW. Keith HootsDeborah BrownGeorge R. BuchananDonna DiMicheleMichael RechtCindy LeissingerShirley BleakAlan CohenPrasad MathewAlison MatsunagaDesiree MedeirosDiane NugentGregory A. ThomasAlexis A. ThompsonKevin McRedmondJ. Michael SoucieHarlan AustinBruce L. EvattThe University of North Carolina at Chapel HillMahidol UniversityUniversity of Colorado School of MedicineUniversity of Colorado Health Sciences CenterEmory UniversityBlood Center of MilwaukeeIndiana Hemophilia and Thrombosis CenterHarvard Medical SchoolRush University Medical CenterUniversity of Texas SystemUniversity of Southwestern Medical CenterWeill Cornell Medical CollegePhoenix Children's HospitalTulane UniversityPrimary Children's Medical CenterUniversity of PennsylvaniaUniversity of New MexicoUCSF Benioff Children's Hospital OaklandUniversity of Hawaii at ManoaCHOC Children`s UC Irvine School of MedicineOregon Health and Science UniversityNorthwestern UniversityPalmetto Health RichlandCenters for Disease Control and Prevention2018-06-112018-06-112012-03-01Gene Therapy. Vol.19, No.3 (2012), 288-29414765462096971282-s2.0-84858005636https://repository.li.mahidol.ac.th/handle/123456789/13796Recombinant 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.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1038/gt.2011.90