O-glycosylated HBsAg peptide can induce specific antibody neutralizing HBV infection

Autor: Atsushi Kuno, Sayuki Iijima, Akira Togayachi, Takashi Sato, Masaaki Korenaga, Hiroki Shimizu, Takanori Wagatsuma, Kiyohiko Angata, Izuru Nagashima, Hiroyuki Kaji, Tatsuhiko Ozawa, Maki Sogabe, Masashi Mizokami, Kazuto Tajiri, Hisashi Narimatsu
Rok vydání: 2022
Předmět:
Zdroj: Biochimica et Biophysica Acta (BBA) - General Subjects. 1866:130020
ISSN: 0304-4165
DOI: 10.1016/j.bbagen.2021.130020
Popis: Background Hepatitis B virus (HBV), which causes hepatitis, liver cirrhosis, and hepatocellular carcinoma, is a global human health problem. HBV contains three envelope proteins, S-, M-, and L-hepatitis B surface antigen (HBsAg). We recently found that O-glycosylated M-HBsAg, reactive with jacalin lectin, is one of the primary components of HBV DNA-containing virus particles. Thus, we aimed to analyze and target the glycosylation of HBsAg. Methods HBsAg prepared from the serum of Japanese patients with HBV were analyzed using mass spectrometry. The glycopeptide modified with O-glycan was generated and used for immunization. The specificity of the generated antibody and the HBV infection inhibition activity was examined. Results Mass spectrometry analysis revealed that T37 and/or T38 on M-HBsAg of genotype C were modulated by ±NeuAc(α2,3)Gal(β1,3)GalNAc. Chemically and enzymatically synthesized O-glycosylated peptide (Glyco-PS2) induced antibodies that recognize mainly PreS2 in M-HBsAg not in L-HBsAg, whereas the non-glycosylated peptide (PS2) induced antisera recognizing L-HBsAg but not O-glycosylated M-HBsAg. The removal of O-glycan from M-HBsAg partly decreased the reactivity of the Glyco-PS2 antibody, suggesting that peptide part was also recognized by the antibody. The antibody further demonstrated the inhibition of HBV infection in human hepatic cells in vitro. Conclusions Glycosylation of HBsAg occurs differently in different HBsAgs in a site-specific manner. The new Glyco-PS2 antibody, recognizing O-glycosylated M-HBsAg of genotype C, could inhibit HBV infection. General significance The detailed analysis of HBsAg identified different glycosylations of HBV surface. The glycosylated peptide based on mass spectrometry analysis showed higher potential to induce functional antibody against HBV.
Databáze: OpenAIRE
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