Functional convergence of a germline-encoded neutralizing antibody response in rhesus macaques immunized with HCV envelope glycoproteins

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Standard

Functional convergence of a germline-encoded neutralizing antibody response in rhesus macaques immunized with HCV envelope glycoproteins. / Chen, Fang; Tzarum, Netanel; Lin, Xiaohe; Giang, Erick; Velázquez-Moctezuma, Rodrigo; Augestad, Elias H.; Nagy, Kenna; He, Linling; Hernandez, Mayda; Fouch, Mallorie E.; Grinyó, Ariadna; Chavez, Deborah; Doranz, Benjamin J.; Prentoe, Jannick; Stanfield, Robyn L.; Lanford, Robert; Bukh, Jens; Wilson, Ian A.; Zhu, Jiang; Law, Mansun.

In: Immunity, Vol. 54, No. 4, 2021, p. 781-796.e4.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Chen, F, Tzarum, N, Lin, X, Giang, E, Velázquez-Moctezuma, R, Augestad, EH, Nagy, K, He, L, Hernandez, M, Fouch, ME, Grinyó, A, Chavez, D, Doranz, BJ, Prentoe, J, Stanfield, RL, Lanford, R, Bukh, J, Wilson, IA, 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

APA

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, 54(4), 781-796.e4. https://doi.org/10.1016/j.immuni.2021.02.013

Vancouver

Chen F, Tzarum N, Lin X, Giang E, Velázquez-Moctezuma R, Augestad EH et al. Functional convergence of a germline-encoded neutralizing antibody response in rhesus macaques immunized with HCV envelope glycoproteins. Immunity. 2021;54(4):781-796.e4. https://doi.org/10.1016/j.immuni.2021.02.013

Author

Chen, Fang ; Tzarum, Netanel ; Lin, Xiaohe ; Giang, Erick ; Velázquez-Moctezuma, Rodrigo ; Augestad, Elias H. ; Nagy, Kenna ; He, Linling ; Hernandez, Mayda ; Fouch, Mallorie E. ; Grinyó, Ariadna ; Chavez, Deborah ; Doranz, Benjamin J. ; Prentoe, Jannick ; Stanfield, Robyn L. ; Lanford, Robert ; Bukh, Jens ; Wilson, Ian A. ; Zhu, Jiang ; Law, Mansun. / Functional convergence of a germline-encoded neutralizing antibody response in rhesus macaques immunized with HCV envelope glycoproteins. In: Immunity. 2021 ; Vol. 54, No. 4. pp. 781-796.e4.

Bibtex

@article{70ddc133873b4de89f2b83b5efb44a3e,
title = "Functional convergence of a germline-encoded neutralizing antibody response in rhesus macaques immunized with HCV envelope glycoproteins",
abstract = "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.",
keywords = "antibody germline, broadly neutralizing antibody, E1E2, E2, Hepatitis C virus, IGHV1-69, immunization, vaccination, VH1-69, VH1.36",
author = "Fang Chen and Netanel Tzarum and Xiaohe Lin and Erick Giang and Rodrigo Vel{\'a}zquez-Moctezuma and Augestad, {Elias H.} and Kenna Nagy and Linling He and Mayda Hernandez and Fouch, {Mallorie E.} and Ariadna Griny{\'o} and Deborah Chavez and Doranz, {Benjamin J.} and Jannick Prentoe and Stanfield, {Robyn L.} and Robert Lanford and Jens Bukh and Wilson, {Ian A.} and Jiang Zhu and Mansun Law",
year = "2021",
doi = "10.1016/j.immuni.2021.02.013",
language = "English",
volume = "54",
pages = "781--796.e4",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "4",

}

RIS

TY - JOUR

T1 - Functional convergence of a germline-encoded neutralizing antibody response in rhesus macaques immunized with HCV envelope glycoproteins

AU - Chen, Fang

AU - Tzarum, Netanel

AU - Lin, Xiaohe

AU - Giang, Erick

AU - Velázquez-Moctezuma, Rodrigo

AU - Augestad, Elias H.

AU - Nagy, Kenna

AU - He, Linling

AU - Hernandez, Mayda

AU - Fouch, Mallorie E.

AU - Grinyó, Ariadna

AU - Chavez, Deborah

AU - Doranz, Benjamin J.

AU - Prentoe, Jannick

AU - Stanfield, Robyn L.

AU - Lanford, Robert

AU - Bukh, Jens

AU - Wilson, Ian A.

AU - Zhu, Jiang

AU - Law, Mansun

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - antibody germline

KW - broadly neutralizing antibody

KW - E1E2

KW - E2

KW - Hepatitis C virus

KW - IGHV1-69

KW - immunization

KW - vaccination

KW - VH1-69

KW - VH1.36

U2 - 10.1016/j.immuni.2021.02.013

DO - 10.1016/j.immuni.2021.02.013

M3 - Journal article

C2 - 33675683

AN - SCOPUS:85104157231

VL - 54

SP - 781-796.e4

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 4

ER -

ID: 260546954