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}
}
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