A single intramuscular injection of an adeno-associated virus (AAV) vector that expresses eCD4-Ig has the potential to treat or prevent HIV-1 infection for a lifetime. eCD4-Ig is a synthetic antibody or ?immunoadhesin? constructed by fusing parts of the viral receptor (CD4) and coreceptor (CCR5) to the constant region of an antibody. Because eCD4-Ig binds the HIV-1 envelope glycoprotein (Env) through the same contacts used by Env to recognize its receptor and coreceptor, eCD4-Ig neutralizes 100% of HIV-1 isolates and presents fundamental barriers to viral escape. We have previously shown that rhesus macaques inoculated with AAV expressing eCD4-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 eCD4-Ig in plasma that are sustained over the long term by AAV-transduced muscle.

Public Health Relevance

The HIV-1 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-1 infection for a lifetime after a single intramuscular injection. Gene transfer vectors that sustain life-long production of eCD4-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 eCD4-Ig for the long-term.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
5R44AI134269-04
Application #
9979748
Study Section
AIDS Discovery and Development of Therapeutics Study Section (ADDT)
Program Officer
Conley, Tony J
Project Start
2017-08-01
Project End
2021-07-31
Budget Start
2020-08-01
Budget End
2021-07-31
Support Year
4
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Emmune, Inc
Department
Type
DUNS #
079628064
City
Juno Beach
State
FL
Country
United States
Zip Code
33408