title: The prevalence of neutralizing antibodies against adeno-associated virus capsids is reduced in young Japanese individuals.
abstract: Pre-existing antibodies against adeno-associated virus (AAV), caused by natural AAV infections, interfere with recombinant AAV vector-mediated gene transfer. We studied the prevalence of neutralizing antibodies against AAV serotypes 1, 2, 5, 8, and 9 in healthy subjects (n = 85) and hemophilia patients (n = 59) in a Japanese population. For healthy subjects, the prevalence of neutralizing antibodies against AAV serotypes 1, 2, 5, 8, and 9 was 36.5%, 35.3%, 37.6%, 32.9%, and 36.5%, respectively, while that in hemophilia patients was 39.7%, 28.8%, 35.6%, 32.9%, and 27.4%, respectively. There was no difference in the prevalence of neutralizing antibody against each AAV serotype between the healthy subjects and the hemophilia patients. The prevalence of neutralizing antibodies against all AAV serotypes increased with age in both healthy subjects and hemophilia patients. High titers of neutralizing antibodies against AAV2 (≥1:224) and AAV8 (≥1:224) were more evident in older individuals (≥42 years old). Approximately 50% of all screened individuals were seronegative for neutralizing antibodies against each AAV tested, while approximately 25% of individuals were seropositive for each AAV serotype tested. The prevalence of seronegativity for all AAV serotypes was 67.0% (healthy subjects, 68.6%; hemophilia patients, 65.0%) and 18.6% (healthy subjects, 20.5%; hemophilia patients, 15.7%) in young (<42 years old) and older subjects (≥42 years old), respectively. The findings from this study suggested that young subjects are more likely to be eligible for gene therapy based on AAV vectors delivered via an intravascular route because of the low prevalence of antibodies to AAV capsids.
authors.affiliation: Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Mimuro
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mizukami
authors.forename: Midori
authors.initials: M
authors.lastname: Shima
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsushita
authors.forename: Masashi
authors.initials: M
authors.lastname: Taki
authors.forename: Shinji
authors.initials: S
authors.lastname: Muto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Higasa
authors.forename: Michio
authors.initials: M
authors.lastname: Sakai
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Ohmori
authors.forename: Seiji
authors.initials: S
authors.lastname: Madoiwa
authors.forename: Keiya
authors.initials: K
authors.lastname: Ozawa
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sakata
mesh_terms: D000328:Adult; D000367:Age Factors; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D044466:Asian People; D002213:Capsid / Q000276:immunology*; D000229:Dependovirus / Q000276:immunology*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008875:Middle Aged; D010322:Parvoviridae Infections / Q000453:epidemiology* / Q000821:virology; D016036:Seroepidemiologic Studies
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral
keywords: AAV vector; epidemiology; gene therapy