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.
Shanghai Institute of Immunology; Institutes of Medical Sciences; Shanghai Jiao Tong University School of Medicine; Shanghai, China.
Wenlong
W
Tan
International Joint Cancer Institute; Second Military Medical University; Shanghai, China.
Yanchun
Y
Meng
PLA General Hospital Cancer Center; PLA School of Medical Sciences; Beijing, China.
Hui
H
Li
PLA General Hospital Cancer Center; PLA School of Medical Sciences; Beijing, China.
Yang
Y
Chen
PLA General Hospital Cancer Center; PLA School of Medical Sciences; Beijing, China.
Siqi
S
Han
PLA General Hospital Cancer Center; PLA School of Medical Sciences; Beijing, China.
Jing
J
Zeng
PLA General Hospital Cancer Center; PLA School of Medical Sciences; Beijing, China.
Ang
A
Huang
International Joint Cancer Institute; Second Military Medical University; Shanghai, China.
Bohua
B
Li
Shanghai Institute of Immunology; Institutes of Medical Sciences; Shanghai Jiao Tong University School of Medicine; Shanghai, China.
Yanyun
Y
Zhang
Shanghai Institute of Immunology; Institutes of Medical Sciences; Shanghai Jiao Tong University School of Medicine; Shanghai, China; International Joint Cancer Institute; Second Military Medical University; Shanghai, China; PLA General Hospital Cancer Center; PLA School of Medical Sciences; Beijing, China.
Yajun
Y
Guo
D000595:Amino Acid Sequence; D018033:Antibodies, Bispecific / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D000939:Epitopes / Q000235:genetics / Q000378:metabolism*; D006514:Hepatitis B Surface Antigens / Q000378:metabolism*; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D010455:Peptides / Q000737:chemistry* / Q000235:genetics
D018033:Antibodies, Bispecific; D000939:Epitopes; D006514:Hepatitis B Surface Antigens; D010455:Peptides
bispecific antibody; conformational change; endocytosis; hepatitis B virus; neutralizing activity; steric hindrance