Neutralization of hepatitis B virus by a novel DNA-encoded monoclonal antibody.

Abstract

Hepatitis B virus (HBV) causes a potentially life-threatening liver infection that frequently results in life-long chronic infection. HBV is responsible for 887,000 deaths each year, most resulting from chronic liver diseases and hepatocellular carcinoma. Presently, there are 250 million chronic HBV carriers worldwide who are at a high risk for developing cirrhosis and hepatocellular carcinoma (HCC). HCC is the most common type of liver cancer with a strong association with HBV infection. HBV transmission through blood transfusions and perinatal transfer from infected mother to child have been common routes of infection. In the present study, we describe the development of a synthetic DNA plasmid encoding an anti-HBV human monoclonal antibody specific for the common "a determinant region" of HBsAg of hepatitis B virus and demonstrate the ability of this platform at directing in vivo antibody expression. In vivo delivery of this DNA encoded monoclonal antibody (DMAb) plasmid in mice resulted in expression of human IgG over a period of one month following a single injection. Serum antibody was found to recognize the relevant conformational epitope from plasma purified native HBsAg as well as bound HBV in HepG2.2.15 cells. The serum DMAb efficiently neutralized HBV and prevented infection of HepaRG cells in vitro. Additional study of these HBV-DMAb as a possible therapy or immunoprophylaxis for HBV infection is warranted.

• Authors: Urvi S Zankharia, Sagar Kudchodkar, Makan Khoshnejad, Alfredo Perales-Puchalt, Hyeree Choi, Michelle Ho, Faraz Zaidi, Kenneth E Ugen, Joseph J Kim, David B Weiner, Kar Muthumani
• Journal: Human vaccines & immunotherapeutics (Hum Vaccin Immunother) Vol. 16 Issue 9 Pg. 2156-2164 (09 01 2020) ISSN: 2164-554X [Electronic] United States
• PMID: 32463327 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• DNA, Viral
• Hepatitis B Surface Antigens

Topics

• Animals
• Antibodies, Monoclonal
• Carcinoma, Hepatocellular
• DNA, Viral (genetics)
• Female
• Hepatitis B (prevention & control)
• Hepatitis B Surface Antigens
• Hepatitis B virus (genetics)
• Infectious Disease Transmission, Vertical
• Liver Neoplasms
• Mice