947. Effects of Natural Pre-Existing Humoral Immunity to AAV on Administration of AAV2-NTN to the Brain of Non-Human Primates

Abstract

The prevalence of antibodies (ab) to wild type AAV2 in humans is estimated to be 50-90%, with 30% developing neutralizing ab (Nab). In an attempt to mimic pre-existing immunity in animal models, many groups have immunized naive animals in order to study its effect on gene transfer. One limitation of this approach is that direct inoculation with high titers of AAV with adjuvant does not mimic the natural course of infection of the wild type virus. Therefore, the nature and intensity of the immune response may differ considerably from that generated by mucosal exposure. In addition, gene transfer is often attempted during the acute phase of the immune response. In contrast, human AAV2 seroconversion typically occurs in childhood, while AAV gene transfer is often performed in adults.