Journal Article

Worldwide Epidemiology of Neutralizing Antibodies to Adeno-Associated Viruses

Vandenberghe, Luk H., Lin, Jianping, Calcedo, Roberto, Gao, Guangping, Wilson, James M.

2009

Overview

Recombinant adeno-associated viruses (AAVs) have unique gene-transfer properties that speak to their potential as carriers for gene therapy or vaccine applications. However, the presence of neutralizing antibodies to AAV as a result of previous exposure can significantly limit effective gene transfer. In this study, we obtained 888 human serum samples from healthy volunteers in 10 countries around the world. Samples were assayed for neutralizing antibodies to AAV1, AAV2, AAV7, and AAV8, as well as to a novel, structurally distinctAAVvector, rh32.33, in an in vitro transduction inhibition assay. Our data revealed that neutralizing antibodies to AAV2 were the most prevalent antibodies in all regions, followed by antibodies to AAV1. The seroprevalences of antibodies to AAV7 and to AAV8 were lower than that for antibodies to AAV1, and neutralization of AAVrh32.33 was only rarely detected. Our data also indicate a strong linkage of seroreactivity between apparently distinct serotypes that has not been predicted previously in animal models.

• Publisher: The University of Chicago Press,University of Chicago Press,Oxford University Press
• Subject: Africa - epidemiology / Antibodies / Antibodies, Viral - blood / Antibodies, Viral - immunology / Australia - epidemiology / Biological and medical sciences / Capsid / Dependovirus / Dependovirus - classification / Dependovirus - genetics / Dependovirus - immunology / Europe - epidemiology / Fundamental and applied biological sciences. Psychology / Gene therapy / Genetic vectors / Global Health / Humans / Infections / Infectious diseases / Medical sciences / Microbiology / Neutralizing antibodies / Parvoviridae Infections - epidemiology / Parvoviridae Infections - immunology / Phylogeny / Seroepidemiologic Studies / United States - epidemiology / Viruses