A bispecific antibody against two different epitopes on hepatitis B surface antigen has potent hepatitis B virus neutralizing activity.
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.
['Tan|Wenlong|W|', 'Meng|Yanchun|Y|', 'Li|Hui|H|', 'Chen|Yang|Y|', 'Han|Siqi|S|', 'Zeng|Jing|J|', 'Huang|Ang|A|', 'Li|Bohua|B|', 'Zhang|Yanyun|Y|', 'Guo|Yajun|Y|']
D000595:Amino Acid Sequence D018033:Antibodies, Bispecific D015153:Blotting, Western D045744:Cell Line, Tumor D000939:Epitopes D006514:Hepatitis B Surface Antigens D006515:Hepatitis B virus D006801:Humans D010455:Peptides
bispecific antibody hepatitis B virus neutralizing activity steric hindrance conformational change endocytosis