In vivo hepatitis B virus-neutralizing activity of an anti-HBsAg humanized antibody in chimpanzees

Abstract

Previously, we constructed a humanized antibody (HuS10) that binds to the common a antigenic determinant on the S protein of HBV. In this study, we evaluated its HBV-neutralizing activity in chimpanzees. A study chimpanzee was intravenously administered with a single dose of HuS10, followed by intravenous challenge with the adr subtype of HBV, while a control chimpanzee was only challenged with the virus. The result showed that the control chimpanzee was infected by the virus, and thus serum HBV surface antigen (HBsAg) became positive from the 14 th to 20 th week and actively acquired serum anti-HBc and anti-HBs antibodies appeared from the 19 th and 23 rd week, respectively. However, in the case of the study chimpanzee, serum HBsAg became positive from the 34 th to 37 th week, while actively acquired serum anti-HBc and anti-HBs antibodies appeared from the 37 th and 40 th week, respectively, indicating that HuS10 neutralized the virus in vivo and thus delayed the HBV infection. This novel humanized antibody will be useful in the immunoprophylaxis of HBV infection.

Sodium taurocholate cotransporting polypeptide inhibition efficiently blocks hepatitis B virus spread in mice with a humanized liver

“…Therefore, new antiviral therapeutic strategies are required. HBV infects a limited number of species, including humans and chimpanzees 2 , but the use of chimpanzees as an infectious model is ethically restricted. Only specific cells, including primary human hepatocytes (PHHs) 3 and HepaRG cells 4 , are susceptible to HBV.…”

Monoclonal Antibodies Against Hepatitis B Viral Surface Antigens and Epitope Grouping

“…(19)(20)(21) However, other studies have suggested that MAbs against the a determinant may or may not be sufficient for the formulation of passively immunized anti-HBS vaccines and for immunodiagnostic purposes. (2,6) For example, in cases where the a determinant demonstrates an altered structure, HBV infection may be poorly detected due to a lack of recognition by MAbs against the a determinant. (6) Therefore, experiments are in progress to generate additional MAbs against the preS1 and preS2 regions of HBsAg, which can then serve as the repertoire for the testing of HBV immunodetection and neutralizing activity in the future.…”

“…Currently, more studies are required to demonstrate that these MAbs exhibit viral neutralizing activity in vivo and can be humanized for use as vaccines or for passive immunization in humans for immunoprophylaxis of HBV infection. (2) The efficacy of these MAbs to neutralize HBV or inhibit the attachment of human hepatocytes as target cells remains to be investigated in the future. Nevertheless, it is reasonable to assume that both the antibody affinity and their respective epitope locations are critical factors during the efficacy evaluation of these anti-HBsAg MAbs.…”

“…(1) This results in at least 600,000 HBV-related deaths annually, most commonly due to cirrhosis, liver failure, or hepatocellular carcinoma. (2,3) A safe and effective vaccine against HBV has been available since 1982 and has drastically decreased the global incidence of HBV infection. (1) However, a variety of problems are associated with the vaccine, including non-response, adverse effects, and the emergence of vaccine escape mutants.…”