Epitope–Paratope Interaction of a Neutralizing Human Anti-Hepatitis B Virus PreS1 Antibody That Recognizes the Receptor-Binding Motif
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-neutraliz...
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MDPI AG
2021-07-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/9/7/754 |
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| author | Jisu Hong Youngjin Choi Yoonjoo Choi Jiwoo Lee Hyo Jeong Hong |
| author_facet | Jisu Hong Youngjin Choi Yoonjoo Choi Jiwoo Lee Hyo Jeong Hong |
| author_sort | Jisu Hong |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T09:20:40Z |
| format | Article |
| id | doaj.art-44123f6f5e1e4e0983f3405de24b1729 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T09:20:40Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-44123f6f5e1e4e0983f3405de24b17292023-11-22T05:12:31ZengMDPI AGVaccines2076-393X2021-07-019775410.3390/vaccines9070754Epitope–Paratope Interaction of a Neutralizing Human Anti-Hepatitis B Virus PreS1 Antibody That Recognizes the Receptor-Binding MotifJisu Hong0Youngjin Choi1Yoonjoo Choi2Jiwoo Lee3Hyo Jeong Hong4Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon 24341, KoreaDepartment of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon 24341, KoreaMedical Research Center, Chonnam National University Medical School, Hwasun 58128, KoreaDepartment of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon 24341, KoreaDepartment of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon 24341, KoreaHepatitis 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.https://www.mdpi.com/2076-393X/9/7/754hepatitis B virushuman monoclonal antibodyvirus entry inhibitorPreS1epitopeparatope |
| spellingShingle | Jisu Hong Youngjin Choi Yoonjoo Choi Jiwoo Lee Hyo Jeong Hong Epitope–Paratope Interaction of a Neutralizing Human Anti-Hepatitis B Virus PreS1 Antibody That Recognizes the Receptor-Binding Motif Vaccines hepatitis B virus human monoclonal antibody virus entry inhibitor PreS1 epitope paratope |
| title | Epitope–Paratope Interaction of a Neutralizing Human Anti-Hepatitis B Virus PreS1 Antibody That Recognizes the Receptor-Binding Motif |
| title_full | Epitope–Paratope Interaction of a Neutralizing Human Anti-Hepatitis B Virus PreS1 Antibody That Recognizes the Receptor-Binding Motif |
| title_fullStr | Epitope–Paratope Interaction of a Neutralizing Human Anti-Hepatitis B Virus PreS1 Antibody That Recognizes the Receptor-Binding Motif |
| title_full_unstemmed | Epitope–Paratope Interaction of a Neutralizing Human Anti-Hepatitis B Virus PreS1 Antibody That Recognizes the Receptor-Binding Motif |
| title_short | Epitope–Paratope Interaction of a Neutralizing Human Anti-Hepatitis B Virus PreS1 Antibody That Recognizes the Receptor-Binding Motif |
| title_sort | epitope paratope interaction of a neutralizing human anti hepatitis b virus pres1 antibody that recognizes the receptor binding motif |
| topic | hepatitis B virus human monoclonal antibody virus entry inhibitor PreS1 epitope paratope |
| url | https://www.mdpi.com/2076-393X/9/7/754 |
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