Alasdair Steven (NIAMS)
Norman Watts (NIAMS)
The invention relates to recombinant chimeric rabbit/human monoclonal antibody fragments (Fabs) against hepatitis B Virus e-antigen (HBeAg), notably Fab me6. Viral hepatitis is the seventh leading cause of death worldwide. Hepatitis B core antigen (HBcAg) forms an icosahedral structure containing the viral genome. Both the HBcAg and the HBeAg of interest here are expressed by two different start codons of the viral C gene. Unlike the related HBcAg which activates type 1 T helper (Th1) cells leading to immune attack, the HBeAg activates Th2 cells which promote immune tolerance. The long-term persistence of HBeAg is associated with the development of hepatocellular carcinoma. Conversely, HBeAg seroconversion (from HBeAg carrier to anti-HBeAg carrier) is a marker for successful therapy of chronically infected patients. The presently phage display engineered antibody Fab me6 shows higher sensitivity and selectivity against HBeAg compared to three commercial diagnostics kits tested; additionally, it also inhibits capsid assembly which is essential for viral replication; furthermore, it can also be fully humanized and has potential for anti-hepatitis B virus therapeutic interventions.
- Hepatocellular carcinoma prophylaxis
- Hepatitis B diagnostics and therapy