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Title: Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection

Abstract

HIV-1-neutralizing antibodies develop in most HIV-1-infected individuals, although highly effective antibodies are generally observed only after years of chronic infection. Here in this paper, we characterize the rate of maturation and extent of diversity for the lineage that produced the broadly neutralizing antibody VRC01 through longitudinal sampling of peripheral B cell transcripts over 15 years and co-crystal structures of lineage members. Next-generation sequencing identified VRC01-lineage transcripts, which encompassed diverse antibodies organized into distinct phylogenetic clades. Prevalent clades maintained characteristic features of antigen recognition, though each evolved binding loops and disulfides that formed distinct recognition surfaces. Over the course of the study period, VRC01-lineage clades showed continuous evolution, with rates of ~2 substitutions per 100 nucleotides per year, comparable to that of HIV-1 evolution. This high rate of antibody evolution provides a mechanism by which antibody lineages can achieve extraordinary diversity and, over years of chronic infection, develop effective HIV-1 neutralization.

Authors:
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Publication Date:
Research Org.:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH)
OSTI Identifier:
1392136
Alternate Identifier(s):
OSTI ID: 1221428
Grant/Contract Number:  
W-31-109-Eng-38; P01-AI104722
Resource Type:
Published Article
Journal Name:
Cell
Additional Journal Information:
Journal Name: Cell Journal Volume: 161 Journal Issue: 3; Journal ID: ISSN 0092-8674
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES

Citation Formats

Wu, Xueling, Zhang, Zhenhai, Schramm, Chaim A., Joyce, M. Gordon, Do Kwon, Young, Zhou, Tongqing, Sheng, Zizhang, Zhang, Baoshan, O’Dell, Sijy, McKee, Krisha, Georgiev, Ivelin S., Chuang, Gwo-Yu, Longo, Nancy S., Lynch, Rebecca M., Saunders, Kevin O., Soto, Cinque, Srivatsan, Sanjay, Yang, Yongping, Bailer, Robert T., Louder, Mark K., Mullikin, James C., Connors, Mark, Kwong, Peter D., Mascola, John R., Shapiro, Lawrence, Benjamin, Betty, Blakesley, Robert, Bouffard, Gerry, Brooks, Shelise, Coleman, Holly, Dekhtyar, Mila, Gregory, Michael, Guan, Xiaobin, Gupta, Jyoti, Han, Joel, Hargrove, April, Ho, Shi-ling, Legaspi, Richelle, Maduro, Quino, Masiello, Cathy, Maskeri, Baishali, McDowell, Jenny, Montemayor, Casandra, Park, Morgan, Riebow, Nancy, Schandler, Karen, Schmidt, Brian, Sison, Christina, Stantripop, Mal, Thomas, James, Thomas, Pam, Vemulapalli, Meg, and Young, Alice. Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection. United States: N. p., 2015. Web. doi:10.1016/j.cell.2015.03.004.
Wu, Xueling, Zhang, Zhenhai, Schramm, Chaim A., Joyce, M. Gordon, Do Kwon, Young, Zhou, Tongqing, Sheng, Zizhang, Zhang, Baoshan, O’Dell, Sijy, McKee, Krisha, Georgiev, Ivelin S., Chuang, Gwo-Yu, Longo, Nancy S., Lynch, Rebecca M., Saunders, Kevin O., Soto, Cinque, Srivatsan, Sanjay, Yang, Yongping, Bailer, Robert T., Louder, Mark K., Mullikin, James C., Connors, Mark, Kwong, Peter D., Mascola, John R., Shapiro, Lawrence, Benjamin, Betty, Blakesley, Robert, Bouffard, Gerry, Brooks, Shelise, Coleman, Holly, Dekhtyar, Mila, Gregory, Michael, Guan, Xiaobin, Gupta, Jyoti, Han, Joel, Hargrove, April, Ho, Shi-ling, Legaspi, Richelle, Maduro, Quino, Masiello, Cathy, Maskeri, Baishali, McDowell, Jenny, Montemayor, Casandra, Park, Morgan, Riebow, Nancy, Schandler, Karen, Schmidt, Brian, Sison, Christina, Stantripop, Mal, Thomas, James, Thomas, Pam, Vemulapalli, Meg, & Young, Alice. Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection. United States. https://doi.org/10.1016/j.cell.2015.03.004
Wu, Xueling, Zhang, Zhenhai, Schramm, Chaim A., Joyce, M. Gordon, Do Kwon, Young, Zhou, Tongqing, Sheng, Zizhang, Zhang, Baoshan, O’Dell, Sijy, McKee, Krisha, Georgiev, Ivelin S., Chuang, Gwo-Yu, Longo, Nancy S., Lynch, Rebecca M., Saunders, Kevin O., Soto, Cinque, Srivatsan, Sanjay, Yang, Yongping, Bailer, Robert T., Louder, Mark K., Mullikin, James C., Connors, Mark, Kwong, Peter D., Mascola, John R., Shapiro, Lawrence, Benjamin, Betty, Blakesley, Robert, Bouffard, Gerry, Brooks, Shelise, Coleman, Holly, Dekhtyar, Mila, Gregory, Michael, Guan, Xiaobin, Gupta, Jyoti, Han, Joel, Hargrove, April, Ho, Shi-ling, Legaspi, Richelle, Maduro, Quino, Masiello, Cathy, Maskeri, Baishali, McDowell, Jenny, Montemayor, Casandra, Park, Morgan, Riebow, Nancy, Schandler, Karen, Schmidt, Brian, Sison, Christina, Stantripop, Mal, Thomas, James, Thomas, Pam, Vemulapalli, Meg, and Young, Alice. Wed . "Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection". United States. https://doi.org/10.1016/j.cell.2015.03.004.
@article{osti_1392136,
title = {Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection},
author = {Wu, Xueling and Zhang, Zhenhai and Schramm, Chaim A. and Joyce, M. Gordon and Do Kwon, Young and Zhou, Tongqing and Sheng, Zizhang and Zhang, Baoshan and O’Dell, Sijy and McKee, Krisha and Georgiev, Ivelin S. and Chuang, Gwo-Yu and Longo, Nancy S. and Lynch, Rebecca M. and Saunders, Kevin O. and Soto, Cinque and Srivatsan, Sanjay and Yang, Yongping and Bailer, Robert T. and Louder, Mark K. and Mullikin, James C. and Connors, Mark and Kwong, Peter D. and Mascola, John R. and Shapiro, Lawrence and Benjamin, Betty and Blakesley, Robert and Bouffard, Gerry and Brooks, Shelise and Coleman, Holly and Dekhtyar, Mila and Gregory, Michael and Guan, Xiaobin and Gupta, Jyoti and Han, Joel and Hargrove, April and Ho, Shi-ling and Legaspi, Richelle and Maduro, Quino and Masiello, Cathy and Maskeri, Baishali and McDowell, Jenny and Montemayor, Casandra and Park, Morgan and Riebow, Nancy and Schandler, Karen and Schmidt, Brian and Sison, Christina and Stantripop, Mal and Thomas, James and Thomas, Pam and Vemulapalli, Meg and Young, Alice},
abstractNote = {HIV-1-neutralizing antibodies develop in most HIV-1-infected individuals, although highly effective antibodies are generally observed only after years of chronic infection. Here in this paper, we characterize the rate of maturation and extent of diversity for the lineage that produced the broadly neutralizing antibody VRC01 through longitudinal sampling of peripheral B cell transcripts over 15 years and co-crystal structures of lineage members. Next-generation sequencing identified VRC01-lineage transcripts, which encompassed diverse antibodies organized into distinct phylogenetic clades. Prevalent clades maintained characteristic features of antigen recognition, though each evolved binding loops and disulfides that formed distinct recognition surfaces. Over the course of the study period, VRC01-lineage clades showed continuous evolution, with rates of ~2 substitutions per 100 nucleotides per year, comparable to that of HIV-1 evolution. This high rate of antibody evolution provides a mechanism by which antibody lineages can achieve extraordinary diversity and, over years of chronic infection, develop effective HIV-1 neutralization.},
doi = {10.1016/j.cell.2015.03.004},
journal = {Cell},
number = 3,
volume = 161,
place = {United States},
year = {Wed Apr 01 00:00:00 EDT 2015},
month = {Wed Apr 01 00:00:00 EDT 2015}
}

Journal Article:
Free Publicly Available Full Text
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https://doi.org/10.1016/j.cell.2015.03.004

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