Functional convergence of a germline-encoded neutralizing antibody response in rhesus macaques immunized with hepatitis C virus envelope glycoproteins
| Autor: | Ariadna Grinyo, Elias H. Augestad, Mayda Hernandez, Netanel Tzarum, Kenna Nagy, Robyn L. Stanfield, Linling He, Mansun Law, Robert E. Lanford, Rodrigo Velázquez-Moctezuma, Deborah Chavez, Xiaohe Lin, Jens Bukh, Erick Giang, Ian A. Wilson, Mallorie E. Fouch, Jannick Prentoe, Benjamin J. Doranz, Jiang Zhu, Fang Chen |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Hepacivirus medicine.disease_cause Epitope antibody germline E1E2 Epitopes 0302 clinical medicine E2 Viral Envelope Proteins Immunology and Allergy Longitudinal Studies Neutralizing antibody chemistry.chemical_classification B-Lymphocytes biology Hepatitis C virus Vaccination Hepatitis C Infectious Diseases 030220 oncology & carcinogenesis Antibody Immunology Somatic hypermutation Receptors Antigen B-Cell CHO Cells immunization Article Cell Line broadly neutralizing antibody 03 medical and health sciences Cricetulus Antibody Repertoire medicine Animals Humans VH1.36 Glycoproteins IGHV1-69 vaccination Virology Antibodies Neutralizing Macaca mulatta 030104 developmental biology Germ Cells HEK293 Cells chemistry Immunization biology.protein Glycoprotein VH1-69 |
| Zdroj: | Immunity Chen, F, Tzarum, N, Lin, X, Giang, E, Velázquez-Moctezuma, R, Augestad, E H, Nagy, K, He, L, Hernandez, M, Fouch, M E, Grinyó, A, Chavez, D, Doranz, B J, Prentoe, J, Stanfield, R L, Lanford, R, Bukh, J, Wilson, I A, Zhu, J & Law, M 2021, ' Functional convergence of a germline-encoded neutralizing antibody response in rhesus macaques immunized with HCV envelope glycoproteins ', Immunity, vol. 54, no. 4, pp. 781-796.e4 . https://doi.org/10.1016/j.immuni.2021.02.013 |
| Popis: | Human IGHV1-69-encoded broadly neutralizing antibodies (bnAbs) that target the hepatitis C virus (HCV) envelope glycoprotein (Env) E2 are important for protection against HCV infection. An IGHV1-69 ortholog gene, VH1.36, is preferentially used for bnAbs isolated from HCV Env-immunized rhesus macaques (RMs). Here, we studied the genetic, structural, and functional properties of VH1.36-encoded bnAbs generated by vaccination, in comparison to IGHV1-69-encoded bnAbs from HCV patients. Global B cell repertoire analysis confirmed the expansion of VH1.36-derived B cells in immunized animals. Most E2-specific, VH1.36-encoded antibodies cross-neutralized HCV. Crystal structures of two RM bnAbs with E2 revealed that the RM bnAbs engaged conserved E2 epitopes using similar molecular features as human bnAbs but with a different binding mode. Longitudinal analyses of the RM antibody repertoire responses during immunization indicated rapid lineage development of VH1.36-encoded bnAbs with limited somatic hypermutation. Our findings suggest functional convergence of a germline-encoded bnAb response to HCV Env with implications for vaccination in humans. |
| Databáze: | OpenAIRE |
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