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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:
 [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1]
  1. The Scripps Research Inst., La Jolla, CA (United States)
Publication Date:
Research Org.:
Argonne National Laboratory (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 Volume: 23; Journal Issue: 11; Journal ID: ISSN 2211-1247
Publisher:
Elsevier
Country of Publication:
United States
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. United States: 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. United States. 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. Tue . "Co-evolution of HIV Envelope and Apex-Targeting Neutralizing Antibody Lineage Provides Benchmarks for Vaccine Design". United States. 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 = {United States},
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

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Cited by: 39 works
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