Development of AAV vectors for long term expression of eCD Ig

ABSTRACT SUMMARY PROJECT DESCRIPTION A single intramuscular injection of an adeno associated virus AAV vector that expresses eCD Ig has the potential to treat or prevent HIV infection for a lifetime eCD Ig is a synthetic antibody or immunoadhesin constructed by fusing parts of the viral receptor CD and coreceptor CCR to the constant region of an antibody Because eCD Ig binds the HIV envelope glycoprotein Env through the same contacts used by Env to recognize its receptor and coreceptor eCD Ig neutralizes of HIV isolates and presents fundamental barriers to viral escape We have previously shown that rhesus macaques inoculated with AAV expressing eCD Ig exhibited sterilizing protection against high dose intravenous challenges with simian human immunodeficiency virus SHIV Now we propose several practical innovations designed to maximize the concentrations of eCD Ig in plasma that are sustained over the long term by AAV transduced muscle PUBLIC HEALTH RELEVANCE STATEMENT The HIV pandemic continues to be a catastrophe for global health and multi billion dollar burden on the US healthcare system This woeful situation could be transformed by the successful development of a product with the potential to treat or prevent HIV infection for a lifetime after a single intramuscular injection Gene transfer vectors that sustain life long production of eCD Ig are being developed by us for this purpose Here we propose several practical innovations that will improve the ability of gene transfer vectors to sustain effective concentrations of eCD Ig for the long term