A sustained high level of endogenously expressed anti-HBs antibody is required to durably block new rounds of infection. HBVtech utilizes an optimized AAV vector that carries human anti-HBs antibody genes to endogenously express human anti-HBs antibody, which is called AAV-anti-HBs vector. When injected into muscle cells, this vector turns skeletal muscle cells into anti-HBs antibody producing cells.
This new HBV therapeutic features three innovations/distinctions.
Unlike exogenous anti-HBs antibody that requires repeated infusions of high doses to maintain therapeutic level, this AAV-anti-HBs vector just needs a single injection to express sustained high level of anti-HBs antibody. Thus, it greatly simplifies HBV cure treatment to a single injection.
Unlike entry inhibitor like Myrcludex B that functions as a ligand to NTCP, an HBV receptor but does not interact with viral particles, thus HBV entry inhibitor can’t prevent HBV particles from attaching hepatocytes. Once attached, the attached viral particles may have a great opportunity to bind neighboring NTCP for viral entry to initiate new round infection, which compromises the competitiveness of entry inhibitor.This understanding is supported by preclinical and clinical studies, which have shown ineffectiveness of entry inhibitor to block new rounds of infection and to induce HBsAg loss in the established HBV infections. This AAV-anti-HBs vector expresses anti-HBs antibody that is against attachment site of viral particles. Once attachment is blocked, there is no virus entry or new rounds of infection. Thus, this AAV-anti-HBs vector delivers far more effective efficacy in blocking new rounds of infection than entry inhibitor.
Unlike therapeutic vaccines that rely on the hosts’ adaptive immunity to deliver therapeutic function and yielded disappointing results in clinical trials, this AAV-anti-HBs vector expresses anti-HBs antibody independent of the adaptive immunity and is expected to express sustained high level of anti-HBs antibody in patients with chronic HBV infection, who are known for defective T and B cell immunity.