Recombinant polyclonal antibody GIGA-2339 potently and pan-genotypically neutralizes hepatitis B virus.

Existing hepatitis B virus (HBV) treatments control viral replication in chronic hepatitis B (CHB) patients but fail to prevent hepatitis B surface antigen (HBsAg) production; excessive HBsAg production leads to HBV-specific immune tolerance. GIGA-2339 is a first-in-class, recombinant polyclonal antibody (pAb) therapeutic consisting of over 1000 human IgG1/IgK antibodies targeting HBsAg epitopes developed for the treatment of chronic HBV infection. As Hepatitis D virus (HDV) utilizes HBsAg produced by HBV for viral entry, GIGA-2339 may also provide benefit to HDV/HBV co-infected patients. Memory B cells from HBV vaccinated donors were isolated and HBsAg-specific antibody sequences were enriched using GigaGen's single cell microfluidic antibody capture platform. Full-length antibody sequences targeting HBsAg were cloned and transfected en masse using a targeted integration Chinese hamster ovary (CHO) cell line, followed by bulk expression and purification. In vitro, GIGA-2339 bound HBsAg and neutralized live HBV with over 2000-fold greater potency than a plasma-based hepatitis B immunoglobulin hyperimmune (HyperHEP B) and slightly lower potency than a HBsAg monoclonal antibody (mAb). GIGA-2339 neutralized pan-genotypic HBsAg (A-H) enveloped viral particles, bound clinically significant HBsAg escape mutants, and engaged human Fc receptors on immune cells. In vivo studies showed improved reduction of circulating HBsAg in a chronic stage as compared to HyperHEP B. The novel polyclonal antibody therapeutic GIGA-2339 potently binds and neutralizes HBsAg to prevent viral infection and to reduce circulating antigen. GIGA-2339 represents an important new therapeutic modality for the CHB treatment landscape and is currently in clinical development.