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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2016
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.
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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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