Cargando…
Co-evolution of HIV Envelope and Apex-Targeting Neutralizing Antibody Lineage Provides Benchmarks for Vaccine Design
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...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019700/ https://www.ncbi.nlm.nih.gov/pubmed/29898396 http://dx.doi.org/10.1016/j.celrep.2018.05.046 |
_version_ | 1783335165414604800 |
---|---|
author | 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. |
author_facet | 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. |
author_sort | Rantalainen, Kimmo |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6019700 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-60197002018-06-28 Co-evolution of HIV Envelope and Apex-Targeting Neutralizing Antibody Lineage Provides Benchmarks for Vaccine Design 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. Cell Rep Article 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. Cell Press 2018-06-13 /pmc/articles/PMC6019700/ /pubmed/29898396 http://dx.doi.org/10.1016/j.celrep.2018.05.046 Text en © 2018 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article 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 |
title | Co-evolution of HIV Envelope and Apex-Targeting Neutralizing Antibody Lineage Provides Benchmarks for Vaccine Design |
title_full | Co-evolution of HIV Envelope and Apex-Targeting Neutralizing Antibody Lineage Provides Benchmarks for Vaccine Design |
title_fullStr | Co-evolution of HIV Envelope and Apex-Targeting Neutralizing Antibody Lineage Provides Benchmarks for Vaccine Design |
title_full_unstemmed | Co-evolution of HIV Envelope and Apex-Targeting Neutralizing Antibody Lineage Provides Benchmarks for Vaccine Design |
title_short | Co-evolution of HIV Envelope and Apex-Targeting Neutralizing Antibody Lineage Provides Benchmarks for Vaccine Design |
title_sort | co-evolution of hiv envelope and apex-targeting neutralizing antibody lineage provides benchmarks for vaccine design |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019700/ https://www.ncbi.nlm.nih.gov/pubmed/29898396 http://dx.doi.org/10.1016/j.celrep.2018.05.046 |
work_keys_str_mv | AT rantalainenkimmo coevolutionofhivenvelopeandapextargetingneutralizingantibodylineageprovidesbenchmarksforvaccinedesign AT berndsenzacharyt coevolutionofhivenvelopeandapextargetingneutralizingantibodylineageprovidesbenchmarksforvaccinedesign AT murrellsasha coevolutionofhivenvelopeandapextargetingneutralizingantibodylineageprovidesbenchmarksforvaccinedesign AT caoliwei coevolutionofhivenvelopeandapextargetingneutralizingantibodylineageprovidesbenchmarksforvaccinedesign AT omorodionoluwarotimi coevolutionofhivenvelopeandapextargetingneutralizingantibodylineageprovidesbenchmarksforvaccinedesign AT torresjonathanl coevolutionofhivenvelopeandapextargetingneutralizingantibodylineageprovidesbenchmarksforvaccinedesign AT wumengyu coevolutionofhivenvelopeandapextargetingneutralizingantibodylineageprovidesbenchmarksforvaccinedesign AT umotoyjeffrey coevolutionofhivenvelopeandapextargetingneutralizingantibodylineageprovidesbenchmarksforvaccinedesign AT coppsjeffrey coevolutionofhivenvelopeandapextargetingneutralizingantibodylineageprovidesbenchmarksforvaccinedesign AT poignardpascal coevolutionofhivenvelopeandapextargetingneutralizingantibodylineageprovidesbenchmarksforvaccinedesign AT landaiselise coevolutionofhivenvelopeandapextargetingneutralizingantibodylineageprovidesbenchmarksforvaccinedesign AT paulsonjamesc coevolutionofhivenvelopeandapextargetingneutralizingantibodylineageprovidesbenchmarksforvaccinedesign AT wilsoniana coevolutionofhivenvelopeandapextargetingneutralizingantibodylineageprovidesbenchmarksforvaccinedesign AT wardandrewb coevolutionofhivenvelopeandapextargetingneutralizingantibodylineageprovidesbenchmarksforvaccinedesign |