SBIR NIAID TOPIC 084: ""ANTIVIRAL DRUGS TO CURE CHRONIC HEPATITIS B VIRUS INFECTION""

Approximately 292 million people are chronically infected with hepatitis Bvirus (HBV) g1oba11y. Current HBV drugs can suppress HBV replication, but can't sustain antiviral efficacy, nor induce anti-HBs Seroconversion, which needs to be achieved for effective HBV cure. But a fundamental problem is that anti-HBs is so low, not even detectable in chronic hepatitisB (CHB) patients, let alone anti-HBs seroconversion. HBVtech is developing AAV vector-based gene therapy to expand endogenous anti-HBs production capacity for effective anti-HBs seroconversion.HBVtech has proven one of two feasibilities required for the success of this drug, i.e. the ability to express sustained high level of anti-HBs in vivo and determined that 4 of 5 AAV­ anti-HBs vectors can express sufficiently high level (rt100ug/ml) of anti-HBs antibodies for at least 25-week in transduced mice. The technical objective of this proposal is to ascertain the 2nd ability that expressed anti- HBs by each of four AAV-anti-HBs vectors can effectively neutralize HBV particles in vitro and in vivo. Upon completion of this project, two leading drug candidates will be ready for phase II development. If successful, this HBV drug in combo with T cell immunity can convert incurable CHB to a curable disease.