4.7 Article

Epitope-Paratope Interaction of a Neutralizing Human Anti-Hepatitis B Virus PreS1 Antibody That Recognizes the Receptor-Binding Motif

Journal

VACCINES
Volume 9, Issue 7, Pages -

Publisher

MDPI
DOI: 10.3390/vaccines9070754

Keywords

hepatitis B virus; human monoclonal antibody; virus entry inhibitor; PreS1; epitope; paratope; receptor-binding motif

Funding

  1. Basic Science Research Program [NRF-2020R1A5A8019180]
  2. Combinatorial Tumor Immunotherapy MRC grant [NRF-2020R1A5A2031185]

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By conducting experiments and structural analysis, it was found that 1A8 can effectively block HBV infection of different genotypes, making it a promising candidate for the prevention and treatment of HBV infection.
Hepatitis B virus (HBV) is a global health burden that causes acute and chronic hepatitis. To develop an HBV-neutralizing antibody that effectively prevents HBV infection, we previously generated a human anti-preS1 monoclonal antibody (1A8) that binds to genotypes A-D and validated its HBV-neutralizing activity in vitro. In the present study, we aimed to determine the fine epitope and paratope of 1A8 to understand the mechanism of HBV neutralization. We performed alanine-scanning mutagenesis on the preS1 (aa 19-34, genotype C) and the heavy (HCDR) and light (LCDR) chain complementarity-determining regions. The 1A8 recognized the three residues (Leu22, Gly23, and Phe25) within the highly conserved receptor-binding motif (NPLGFFP) of the preS1, while four CDR residues of 1A8 were critical in antigen binding. Structural analysis of the epitope-paratope interaction by molecular modeling revealed that Leu100 in the HCDR3, Ala50 in the HCDR2, and Tyr96 in the LCDR3 closely interacted with Leu22, Gly23, and Phe25 of the preS1. Additionally, we found that 1A8 also binds to the receptor-binding motif (NPLGFLP) of infrequently occurring HBV. The results suggest that 1A8 may broadly and effectively block HBV entry and thus have potential as a promising candidate for the prevention and treatment of HBV infection.

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