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HIV Vaccine Design to Target Germline Precursors of Glycan-Dependent Broadly Neutralizing Antibodies
Broadly neutralizing antibodies (bnAbs) against the N332 supersite of the HIV envelope (Env) trimer are the most common bnAbs induced during infection, making them promising leads for vaccine design. Wild-type Env glycoproteins lack detectable affinity for supersite-bnAb germline precursors and are...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5040827/ https://www.ncbi.nlm.nih.gov/pubmed/27617678 http://dx.doi.org/10.1016/j.immuni.2016.08.016 |
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author | Steichen, Jon M. Kulp, Daniel W. Tokatlian, Talar Escolano, Amelia Dosenovic, Pia Stanfield, Robyn L. McCoy, Laura E. Ozorowski, Gabriel Hu, Xiaozhen Kalyuzhniy, Oleksandr Briney, Bryan Schiffner, Torben Garces, Fernando Freund, Natalia T. Gitlin, Alexander D. Menis, Sergey Georgeson, Erik Kubitz, Michael Adachi, Yumiko Jones, Meaghan Mutafyan, Andrew A. Yun, Dong Soo Mayer, Christian T. Ward, Andrew B. Burton, Dennis R. Wilson, Ian A. Irvine, Darrell J. Nussenzweig, Michel C. Schief, William R. |
author_facet | Steichen, Jon M. Kulp, Daniel W. Tokatlian, Talar Escolano, Amelia Dosenovic, Pia Stanfield, Robyn L. McCoy, Laura E. Ozorowski, Gabriel Hu, Xiaozhen Kalyuzhniy, Oleksandr Briney, Bryan Schiffner, Torben Garces, Fernando Freund, Natalia T. Gitlin, Alexander D. Menis, Sergey Georgeson, Erik Kubitz, Michael Adachi, Yumiko Jones, Meaghan Mutafyan, Andrew A. Yun, Dong Soo Mayer, Christian T. Ward, Andrew B. Burton, Dennis R. Wilson, Ian A. Irvine, Darrell J. Nussenzweig, Michel C. Schief, William R. |
author_sort | Steichen, Jon M. |
collection | PubMed |
description | Broadly neutralizing antibodies (bnAbs) against the N332 supersite of the HIV envelope (Env) trimer are the most common bnAbs induced during infection, making them promising leads for vaccine design. Wild-type Env glycoproteins lack detectable affinity for supersite-bnAb germline precursors and are therefore unsuitable immunogens to prime supersite-bnAb responses. We employed mammalian cell surface display to design stabilized Env trimers with affinity for germline-reverted precursors of PGT121-class supersite bnAbs. The trimers maintained native-like antigenicity and structure, activated PGT121 inferred-germline B cells ex vivo when multimerized on liposomes, and primed PGT121-like responses in PGT121 inferred-germline knockin mice. Design intermediates have levels of epitope modification between wild-type and germline-targeting trimers; their mutation gradient suggests sequential immunization to induce bnAbs, in which the germline-targeting prime is followed by progressively less-mutated design intermediates and, lastly, with native trimers. The vaccine design strategies described could be utilized to target other epitopes on HIV or other pathogens. |
format | Online Article Text |
id | pubmed-5040827 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-50408272016-09-30 HIV Vaccine Design to Target Germline Precursors of Glycan-Dependent Broadly Neutralizing Antibodies Steichen, Jon M. Kulp, Daniel W. Tokatlian, Talar Escolano, Amelia Dosenovic, Pia Stanfield, Robyn L. McCoy, Laura E. Ozorowski, Gabriel Hu, Xiaozhen Kalyuzhniy, Oleksandr Briney, Bryan Schiffner, Torben Garces, Fernando Freund, Natalia T. Gitlin, Alexander D. Menis, Sergey Georgeson, Erik Kubitz, Michael Adachi, Yumiko Jones, Meaghan Mutafyan, Andrew A. Yun, Dong Soo Mayer, Christian T. Ward, Andrew B. Burton, Dennis R. Wilson, Ian A. Irvine, Darrell J. Nussenzweig, Michel C. Schief, William R. Immunity Article Broadly neutralizing antibodies (bnAbs) against the N332 supersite of the HIV envelope (Env) trimer are the most common bnAbs induced during infection, making them promising leads for vaccine design. Wild-type Env glycoproteins lack detectable affinity for supersite-bnAb germline precursors and are therefore unsuitable immunogens to prime supersite-bnAb responses. We employed mammalian cell surface display to design stabilized Env trimers with affinity for germline-reverted precursors of PGT121-class supersite bnAbs. The trimers maintained native-like antigenicity and structure, activated PGT121 inferred-germline B cells ex vivo when multimerized on liposomes, and primed PGT121-like responses in PGT121 inferred-germline knockin mice. Design intermediates have levels of epitope modification between wild-type and germline-targeting trimers; their mutation gradient suggests sequential immunization to induce bnAbs, in which the germline-targeting prime is followed by progressively less-mutated design intermediates and, lastly, with native trimers. The vaccine design strategies described could be utilized to target other epitopes on HIV or other pathogens. Cell Press 2016-09-20 /pmc/articles/PMC5040827/ /pubmed/27617678 http://dx.doi.org/10.1016/j.immuni.2016.08.016 Text en © 2016 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 Steichen, Jon M. Kulp, Daniel W. Tokatlian, Talar Escolano, Amelia Dosenovic, Pia Stanfield, Robyn L. McCoy, Laura E. Ozorowski, Gabriel Hu, Xiaozhen Kalyuzhniy, Oleksandr Briney, Bryan Schiffner, Torben Garces, Fernando Freund, Natalia T. Gitlin, Alexander D. Menis, Sergey Georgeson, Erik Kubitz, Michael Adachi, Yumiko Jones, Meaghan Mutafyan, Andrew A. Yun, Dong Soo Mayer, Christian T. Ward, Andrew B. Burton, Dennis R. Wilson, Ian A. Irvine, Darrell J. Nussenzweig, Michel C. Schief, William R. HIV Vaccine Design to Target Germline Precursors of Glycan-Dependent Broadly Neutralizing Antibodies |
title | HIV Vaccine Design to Target Germline Precursors of Glycan-Dependent Broadly Neutralizing Antibodies |
title_full | HIV Vaccine Design to Target Germline Precursors of Glycan-Dependent Broadly Neutralizing Antibodies |
title_fullStr | HIV Vaccine Design to Target Germline Precursors of Glycan-Dependent Broadly Neutralizing Antibodies |
title_full_unstemmed | HIV Vaccine Design to Target Germline Precursors of Glycan-Dependent Broadly Neutralizing Antibodies |
title_short | HIV Vaccine Design to Target Germline Precursors of Glycan-Dependent Broadly Neutralizing Antibodies |
title_sort | hiv vaccine design to target germline precursors of glycan-dependent broadly neutralizing antibodies |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5040827/ https://www.ncbi.nlm.nih.gov/pubmed/27617678 http://dx.doi.org/10.1016/j.immuni.2016.08.016 |
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