DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

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. https://doi.org/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. https://doi.org/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
https://doi.org/10.1016/j.celrep.2018.05.046

Citation Metrics:
Cited by: 9 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Viral Persistence: HIV's Strategies of Immune System Evasion
journal, February 2002


Cell- and Protein-Directed Glycosylation of Native Cleaved HIV-1 Envelope
journal, June 2015

  • Pritchard, Laura K.; Harvey, David J.; Bonomelli, Camille
  • Journal of Virology, Vol. 89, Issue 17
  • DOI: 10.1128/JVI.01190-15

Accelerated cryo-EM structure determination with parallelisation using GPUs in RELION-2
journal, November 2016

  • Kimanius, Dari; Forsberg, Björn O.; Scheres, Sjors HW
  • eLife, Vol. 5
  • DOI: 10.7554/eLife.18722

Targeted N-glycan deletion at the receptor-binding site retains HIV Env NFL trimer integrity and accelerates the elicited antibody response
journal, September 2017


Thermostability of Well-Ordered HIV Spikes Correlates with the Elicitation of Autologous Tier 2 Neutralizing Antibodies
journal, August 2016


Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9
journal, November 2011

  • McLellan, Jason S.; Pancera, Marie; Carrico, Chris
  • Nature, Vol. 480, Issue 7377
  • DOI: 10.1038/nature10696

Broadly Neutralizing Antibody Responses in a Large Longitudinal Sub-Saharan HIV Primary Infection Cohort
journal, January 2016


Native-like Env trimers as a platform for HIV-1 vaccine design
journal, January 2017

  • Sanders, Rogier W.; Moore, John P.
  • Immunological Reviews, Vol. 275, Issue 1
  • DOI: 10.1111/imr.12481

Broad neutralization coverage of HIV by multiple highly potent antibodies
journal, September 2011

  • Walker, Laura M.; Huber, Michael; Doores, Katie J.
  • Nature, Vol. 477, Issue 7365
  • DOI: 10.1038/nature10373

Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design
journal, May 2016


DoG Picker and TiltPicker: Software tools to facilitate particle selection in single particle electron microscopy
journal, May 2009

  • Voss, N. R.; Yoshioka, C. K.; Radermacher, M.
  • Journal of Structural Biology, Vol. 166, Issue 2
  • DOI: 10.1016/j.jsb.2009.01.004

Structural Delineation of a Quaternary, Cleavage-Dependent Epitope at the gp41-gp120 Interface on Intact HIV-1 Env Trimers
journal, May 2014


The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling
journal, November 2005


Tailored Immunogens Direct Affinity Maturation toward HIV Neutralizing Antibodies
journal, September 2016


Atomic-accuracy models from 4.5-Å cryo-electron microscopy data with density-guided iterative local refinement
journal, February 2015

  • DiMaio, Frank; Song, Yifan; Li, Xueming
  • Nature Methods, Vol. 12, Issue 4
  • DOI: 10.1038/nmeth.3286

Towards automated crystallographic structure refinement with phenix.refine
journal, March 2012

  • Afonine, Pavel V.; Grosse-Kunstleve, Ralf W.; Echols, Nathaniel
  • Acta Crystallographica Section D Biological Crystallography, Vol. 68, Issue 4
  • DOI: 10.1107/S0907444912001308

A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but Not Non-Neutralizing Antibodies
journal, September 2013


Native Conformation and Canonical Disulfide Bond Formation Are Interlinked Properties of HIV-1 Env Glycoproteins
journal, December 2015

  • Go, Eden P.; Cupo, Albert; Ringe, Rajesh
  • Journal of Virology, Vol. 90, Issue 6
  • DOI: 10.1128/JVI.01953-15

Rational HIV Immunogen Design to Target Specific Germline B Cell Receptors
journal, March 2013


New Member of the V1V2-Directed CAP256-VRC26 Lineage That Shows Increased Breadth and Exceptional Potency
journal, October 2015

  • Doria-Rose, Nicole A.; Bhiman, Jinal N.; Roark, Ryan S.
  • Journal of Virology, Vol. 90, Issue 1
  • DOI: 10.1128/JVI.01791-15

Automated Identification of Amino Acid Sequence Variations in Proteins by HPLC/Microspray Tandem Mass Spectrometry
journal, February 2000

  • Gatlin, Christine L.; Eng, Jimmy K.; Cross, Stacy T.
  • Analytical Chemistry, Vol. 72, Issue 4
  • DOI: 10.1021/ac991025n

An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database
journal, November 1994

  • Eng, Jimmy K.; McCormack, Ashley L.; Yates, John R.
  • Journal of the American Society for Mass Spectrometry, Vol. 5, Issue 11
  • DOI: 10.1016/1044-0305(94)80016-2

Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex
journal, November 2014

  • Sok, Devin; van Gils, Marit J.; Pauthner, Matthias
  • Proceedings of the National Academy of Sciences, Vol. 111, Issue 49
  • DOI: 10.1073/pnas.1415789111

MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy
journal, February 2017

  • Zheng, Shawn Q.; Palovcak, Eugene; Armache, Jean-Paul
  • Nature Methods, Vol. 14, Issue 4
  • DOI: 10.1038/nmeth.4193

UCSF Chimera?A visualization system for exploratory research and analysis
journal, January 2004

  • Pettersen, Eric F.; Goddard, Thomas D.; Huang, Conrad C.
  • Journal of Computational Chemistry, Vol. 25, Issue 13
  • DOI: 10.1002/jcc.20084

Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody
journal, April 2016


HIV-1 neutralizing antibodies induced by native-like envelope trimers
journal, June 2015


Gctf: Real-time CTF determination and correction
journal, January 2016


HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen
journal, March 2016


Holes in the Glycan Shield of the Native HIV Envelope Are a Target of Trimer-Elicited Neutralizing Antibodies
journal, August 2016


Sequential and Simultaneous Immunization of Rabbits with HIV-1 Envelope Glycoprotein SOSIP.664 Trimers from Clades A, B and C
journal, September 2016


Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein
journal, March 2016


Immunogenicity of a Prefusion HIV-1 Envelope Trimer in Complex with a Quaternary-Structure-Specific Antibody
journal, December 2015

  • Cheng, Cheng; Pancera, Marie; Bossert, Adam
  • Journal of Virology, Vol. 90, Issue 6
  • DOI: 10.1128/JVI.02380-15

MolProbity : all-atom structure validation for macromolecular crystallography
journal, December 2009

  • Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1
  • DOI: 10.1107/S0907444909042073

Broad and Potent Neutralizing Antibodies from an African Donor Reveal a New HIV-1 Vaccine Target
journal, September 2009


Global site-specific N-glycosylation analysis of HIV envelope glycoprotein
journal, March 2017

  • Cao, Liwei; Diedrich, Jolene K.; Kulp, Daniel W.
  • Nature Communications, Vol. 8, Issue 1
  • DOI: 10.1038/ncomms14954

Features and development of Coot
journal, March 2010

  • Emsley, P.; Lohkamp, B.; Scott, W. G.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
  • DOI: 10.1107/S0907444910007493

EMRinger: side chain–directed model and map validation for 3D cryo-electron microscopy
journal, August 2015

  • Barad, Benjamin A.; Echols, Nathaniel; Wang, Ray Yu-Ruei
  • Nature Methods, Vol. 12, Issue 10
  • DOI: 10.1038/nmeth.3541

DTASelect and Contrast:  Tools for Assembling and Comparing Protein Identifications from Shotgun Proteomics
journal, February 2002

  • Tabb, David L.; McDonald, W. Hayes; Yates, John R.
  • Journal of Proteome Research, Vol. 1, Issue 1, p. 21-26
  • DOI: 10.1021/pr015504q

UCSF ChimeraX: Meeting modern challenges in visualization and analysis: UCSF ChimeraX Visualization System
journal, September 2017

  • Goddard, Thomas D.; Huang, Conrad C.; Meng, Elaine C.
  • Protein Science, Vol. 27, Issue 1
  • DOI: 10.1002/pro.3235

Semi-automated selection of cryo-EM particles in RELION-1.3
journal, February 2015


PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010

  • Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
  • DOI: 10.1107/S0907444909052925

Sequential Immunization Elicits Broadly Neutralizing Anti-HIV-1 Antibodies in Ig Knockin Mice
journal, September 2016


Leginon: a system for fully automated acquisition of 1000 electron micrographs a day
journal, July 1999


Structural Evolution of Glycan Recognition by a Family of Potent HIV Antibodies
journal, September 2014


Cryo-EM structure of a native, fully glycosylated, cleaved HIV-1 envelope trimer
journal, March 2016


Glycans Function as Anchors for Antibodies and Help Drive HIV Broadly Neutralizing Antibody Development
journal, November 2017


Germline-targeting immunogens
journal, January 2017

  • Stamatatos, Leonidas; Pancera, Marie; McGuire, Andrew T.
  • Immunological Reviews, Vol. 275, Issue 1
  • DOI: 10.1111/imr.12483

HIV Vaccine Design to Target Germline Precursors of Glycan-Dependent Broadly Neutralizing Antibodies
journal, September 2016


ProLuCID: An improved SEQUEST-like algorithm with enhanced sensitivity and specificity
journal, November 2015


[20] Processing of X-ray diffraction data collected in oscillation mode
book, January 1997


Phaser crystallographic software
journal, July 2007

  • McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.
  • Journal of Applied Crystallography, Vol. 40, Issue 4
  • DOI: 10.1107/S0021889807021206