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Title: Co-evolution of HIV Envelope and Apex-Targeting Neutralizing Antibody Lineage Provides Benchmarks for Vaccine Design

Abstract

Broadly neutralizing antibodies (bnAbs) targeting the HIV envelope glycoprotein (Env) typically take years to develop. Longitudinal analyses of both neutralizing antibody lineages and viruses at serial time points during infection provide a basis for understanding the co-evolutionary contest between HIV and the humoral immune system. Here, we describe the structural characterization of an apex-targeting antibody lineage and autologous clade A viral Env from a donor in the Protocol C cohort. Comparison of Ab-Env complexes at early and late time points reveals that, within the antibody lineage, the CDRH3 loop rigidifies, the bnAb angle of approach steepens, and surface charges are mutated to accommodate glycan changes. Additionally, we observed differences in site-specific glycosylation between soluble and full-length Env constructs, which may be important for tuning optimal immunogenicity in soluble Env trimers. These studies therefore provide important guideposts for design of immunogens that prime and mature nAb responses to the Env V2-apex.

Authors:
; ; ; ; ; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES); USDOE Office of Science (SC), Biological and Environmental Research (BER); National Inst. of General Medical Sciences; National Institutes of Health (NIH)
OSTI Identifier:
1454274
Alternate Identifier(s):
OSTI ID: 1502216
Grant/Contract Number:  
AC02-76SF00515; AC02-06CH11357; P41GM103393; UM1 AI100663; OPP1115782; OPP1084519
Resource Type:
Published Article
Journal Name:
Cell Reports
Additional Journal Information:
Journal Name: Cell Reports Journal Volume: 23 Journal Issue: 11; Journal ID: ISSN 2211-1247
Publisher:
Elsevier
Country of Publication:
Netherlands
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; broadly neutralizing antibody; HIV; evolution; Protocol C; cryo-EM; structure

Citation Formats

Rantalainen, Kimmo, Berndsen, Zachary T., Murrell, Sasha, Cao, Liwei, Omorodion, Oluwarotimi, Torres, Jonathan L., Wu, Mengyu, Umotoy, Jeffrey, Copps, Jeffrey, Poignard, Pascal, Landais, Elise, Paulson, James C., Wilson, Ian A., and Ward, Andrew B. Co-evolution of HIV Envelope and Apex-Targeting Neutralizing Antibody Lineage Provides Benchmarks for Vaccine Design. Netherlands: N. p., 2018. Web. doi:10.1016/j.celrep.2018.05.046.
Rantalainen, Kimmo, Berndsen, Zachary T., Murrell, Sasha, Cao, Liwei, Omorodion, Oluwarotimi, Torres, Jonathan L., Wu, Mengyu, Umotoy, Jeffrey, Copps, Jeffrey, Poignard, Pascal, Landais, Elise, Paulson, James C., Wilson, Ian A., & Ward, Andrew B. Co-evolution of HIV Envelope and Apex-Targeting Neutralizing Antibody Lineage Provides Benchmarks for Vaccine Design. Netherlands. doi:10.1016/j.celrep.2018.05.046.
Rantalainen, Kimmo, Berndsen, Zachary T., Murrell, Sasha, Cao, Liwei, Omorodion, Oluwarotimi, Torres, Jonathan L., Wu, Mengyu, Umotoy, Jeffrey, Copps, Jeffrey, Poignard, Pascal, Landais, Elise, Paulson, James C., Wilson, Ian A., and Ward, Andrew B. Fri . "Co-evolution of HIV Envelope and Apex-Targeting Neutralizing Antibody Lineage Provides Benchmarks for Vaccine Design". Netherlands. doi:10.1016/j.celrep.2018.05.046.
@article{osti_1454274,
title = {Co-evolution of HIV Envelope and Apex-Targeting Neutralizing Antibody Lineage Provides Benchmarks for Vaccine Design},
author = {Rantalainen, Kimmo and Berndsen, Zachary T. and Murrell, Sasha and Cao, Liwei and Omorodion, Oluwarotimi and Torres, Jonathan L. and Wu, Mengyu and Umotoy, Jeffrey and Copps, Jeffrey and Poignard, Pascal and Landais, Elise and Paulson, James C. and Wilson, Ian A. and Ward, Andrew B.},
abstractNote = {Broadly neutralizing antibodies (bnAbs) targeting the HIV envelope glycoprotein (Env) typically take years to develop. Longitudinal analyses of both neutralizing antibody lineages and viruses at serial time points during infection provide a basis for understanding the co-evolutionary contest between HIV and the humoral immune system. Here, we describe the structural characterization of an apex-targeting antibody lineage and autologous clade A viral Env from a donor in the Protocol C cohort. Comparison of Ab-Env complexes at early and late time points reveals that, within the antibody lineage, the CDRH3 loop rigidifies, the bnAb angle of approach steepens, and surface charges are mutated to accommodate glycan changes. Additionally, we observed differences in site-specific glycosylation between soluble and full-length Env constructs, which may be important for tuning optimal immunogenicity in soluble Env trimers. These studies therefore provide important guideposts for design of immunogens that prime and mature nAb responses to the Env V2-apex.},
doi = {10.1016/j.celrep.2018.05.046},
journal = {Cell Reports},
number = 11,
volume = 23,
place = {Netherlands},
year = {2018},
month = {6}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.1016/j.celrep.2018.05.046

Citation Metrics:
Cited by: 9 works
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Works referencing / citing this record:

Development of broadly neutralizing antibodies in HIV-1 infected elite neutralizers
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  • Wibmer, Constantinos Kurt; Richardson, Simone I.; Yolitz, Jason
  • Nature Communications, Vol. 9, Issue 1
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Disruption of the HIV-1 Envelope allosteric network blocks CD4-induced rearrangements
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Recent progress in broadly neutralizing antibodies to HIV
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Stabilization of the V2 loop improves the presentation of V2 loop–associated broadly neutralizing antibody epitopes on HIV-1 envelope trimers
journal, February 2019

  • de Taeye, Steven W.; Go, Eden P.; Sliepen, Kwinten
  • Journal of Biological Chemistry, Vol. 294, Issue 14
  • DOI: 10.1074/jbc.ra118.005396

Strategies for inducing effective neutralizing antibody responses against HIV-1
journal, November 2019


Immunodominance and Antigenic Variation of Influenza Virus Hemagglutinin: Implications for Design of Universal Vaccine Immunogens
journal, April 2019

  • Zost, Seth J.; Wu, Nicholas C.; Hensley, Scott E.
  • The Journal of Infectious Diseases, Vol. 219, Issue Supplement_1
  • DOI: 10.1093/infdis/jiy696

Closing and Opening Holes in the Glycan Shield of HIV-1 Envelope Glycoprotein SOSIP Trimers Can Redirect the Neutralizing Antibody Response to the Newly Unmasked Epitopes
journal, November 2018

  • Ringe, Rajesh P.; Pugach, Pavel; Cottrell, Christopher A.
  • Journal of Virology, Vol. 93, Issue 4
  • DOI: 10.1128/jvi.01656-18

Similarities and differences between native HIV-1 envelope glycoprotein trimers and stabilized soluble trimer mimetics
journal, July 2019

  • Torrents de la Peña, Alba; Rantalainen, Kimmo; Cottrell, Christopher A.
  • PLOS Pathogens, Vol. 15, Issue 7
  • DOI: 10.1371/journal.ppat.1007920