Journal
MABS
Volume 5, Issue 6, Pages 946-955Publisher
LANDES BIOSCIENCE
DOI: 10.4161/mabs.26390
Keywords
hepatitis B virus; bispecific antibody; neutralizing activity; steric hindrance; conformational change; endocytosis
Categories
Funding
- National Natural Science Foundation of China
- National Key Project for Infectious Diseases [2012ZX10002012-009]
- Ministry of Science and Technology of China
- Shanghai Commission of Science and Technology
- Shanghai Leading Academic Discipline Project [B905]
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Treatment of chronic hepatitis B virus (HBV) infection with interferon and viral reverse transcriptase inhibitor regimens results in poor viral clearance, loss of response, and emergence of drug-resistant mutant virus strains. These problems continue to drive the development of new therapeutic approaches to combat HBV. Here, we engineered a bispecific antibody using two monoclonal antibodies cloned from hepatitis B surface antigen (HBsAg)-specific memory B cells from recombinant HBsAg-vaccinated healthy volunteers. Next, we evaluated its efficacy in neutralizing HBV in HepaRG cells. This bispecific antibody, denoted as C4D2-BsAb, had superior HBV-neutralizing activity compared with the combination of both parental monoclonal antibodies, possibly through steric hindrance or induction of HBsAg conformational changes. Moreover, C4D2-BsAb has superior endocytotic characteristics into hepatocytes, which inhibits the secretion of HBsAg. These results suggest that the anti-HBsAg bispecific antibody may be an effective treatment method against HBV infection.
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