Hepatitis B Immunoglobulin Inhibits The Secretion of HBV Via Antigen-Antibody Precipitation in The Multivesicular Body

Although the main action of human hepatitis B immunoglobulin (HBIG) of neutralizing the hepatitis B virus surface antigen (HBsAg) in the serum is known, HBIG is known to be localized in the cell. However, the effect of intracellularly located HBIG is not well elucidated due to the low purity of conventional plasma-derived HBIG (cHBIG). We attempted to clarify the mechanism of action of internalized HBIG using recombinant HBIG (lenvervimab). We used HBsAg cell lines, non-HBsAg cell lines and human HBsAg-producing hepatocytes. Autophagosome lysis pathway related proteins and Rab5, calnexin, giantin, and Rab7 were used to localize HBsAg and anti-HBs-IgG in the cytoplasm with Western blot and confocal microscopy.Intracellular anti-HBs-IgG (lenvervimab and cHBIG) transported by Fc receptor-mediated endocytosis increased the autophagosomes, but there was no change in autolysis. HBsAg and anti-HBs-IgG precipitated in the cytoplasm and co-localized in the multivesicular body. HBsAg secretion in the culture medium was decreased after lenvervimab. Simultaneously, the amount of cellular HBsAg increased in the cell lines but decreased in the human hepatocytes. Furthermore, intracellular lenvervimab was not easily washed out only in the HBsAg cell lines.Lenvervimab decreases the secretion of HBsAg, and HBsAg-antibody precipitation in the multivesicular body might play an important role.