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author Bricault, Christine A.
Yusim, Karina
Seaman, Michael S.
Yoon, Hyejin
Theiler, James
Giorgi, Elena E.
Wagh, Kshitij
Theiler, Maxwell
Hraber, Peter
Macke, Jennifer P.
Kreider, Edward F.
Learn, Gerald H.
Hahn, Beatrice H.
Scheid, Johannes F.
Kovacs, James M.
Shields, Jennifer L.
Lavine, Christy L.
Ghantous, Fadi
Rist, Michael
Bayne, Madeleine G.
Neubauer, George H.
McMahan, Katherine
Peng, Hanqin
Chéneau, Coraline
Jones, Jennifer J.
Zeng, Jie
Ochsenbauer, Christina
Nkolola, Joseph P.
Stephenson, Kathryn E.
Chen, Bing
Gnanakaran, S.
Bonsignori, Mattia
Williams, LaTonya D.
Haynes, Barton F.
Doria-Rose, Nicole
Mascola, John R.
Montefiori, David C.
Barouch, Dan H.
Korber, Bette
author_facet Bricault, Christine A.
Yusim, Karina
Seaman, Michael S.
Yoon, Hyejin
Theiler, James
Giorgi, Elena E.
Wagh, Kshitij
Theiler, Maxwell
Hraber, Peter
Macke, Jennifer P.
Kreider, Edward F.
Learn, Gerald H.
Hahn, Beatrice H.
Scheid, Johannes F.
Kovacs, James M.
Shields, Jennifer L.
Lavine, Christy L.
Ghantous, Fadi
Rist, Michael
Bayne, Madeleine G.
Neubauer, George H.
McMahan, Katherine
Peng, Hanqin
Chéneau, Coraline
Jones, Jennifer J.
Zeng, Jie
Ochsenbauer, Christina
Nkolola, Joseph P.
Stephenson, Kathryn E.
Chen, Bing
Gnanakaran, S.
Bonsignori, Mattia
Williams, LaTonya D.
Haynes, Barton F.
Doria-Rose, Nicole
Mascola, John R.
Montefiori, David C.
Barouch, Dan H.
Korber, Bette
author_sort Bricault, Christine A.
collection PubMed
description Eliciting HIV-1-specific broadly neutralizing antibodies (bNAbs) remains a challenge for vaccine development, and the potential of passively delivered bNAbs for prophylaxis and therapeutics is being explored. We used neutralization data from four large virus panels to comprehensively map viral signatures associated with bNAb sensitivity, including amino acids, hypervariable region characteristics, and clade effects across four different classes of bNAbs. The bNAb signatures defined for the variable loop 2 (V2) epitope region of HIV-1 Env were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine, and immunization of guinea pigs with V2-SET vaccines resulted in increased breadth of NAb responses compared with Env 459C alone. These data demonstrate that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens capable of eliciting antibody responses with greater neutralization breadth.
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spelling pubmed-63313412019-01-22 HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design Bricault, Christine A. Yusim, Karina Seaman, Michael S. Yoon, Hyejin Theiler, James Giorgi, Elena E. Wagh, Kshitij Theiler, Maxwell Hraber, Peter Macke, Jennifer P. Kreider, Edward F. Learn, Gerald H. Hahn, Beatrice H. Scheid, Johannes F. Kovacs, James M. Shields, Jennifer L. Lavine, Christy L. Ghantous, Fadi Rist, Michael Bayne, Madeleine G. Neubauer, George H. McMahan, Katherine Peng, Hanqin Chéneau, Coraline Jones, Jennifer J. Zeng, Jie Ochsenbauer, Christina Nkolola, Joseph P. Stephenson, Kathryn E. Chen, Bing Gnanakaran, S. Bonsignori, Mattia Williams, LaTonya D. Haynes, Barton F. Doria-Rose, Nicole Mascola, John R. Montefiori, David C. Barouch, Dan H. Korber, Bette Cell Host Microbe Article Eliciting HIV-1-specific broadly neutralizing antibodies (bNAbs) remains a challenge for vaccine development, and the potential of passively delivered bNAbs for prophylaxis and therapeutics is being explored. We used neutralization data from four large virus panels to comprehensively map viral signatures associated with bNAb sensitivity, including amino acids, hypervariable region characteristics, and clade effects across four different classes of bNAbs. The bNAb signatures defined for the variable loop 2 (V2) epitope region of HIV-1 Env were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine, and immunization of guinea pigs with V2-SET vaccines resulted in increased breadth of NAb responses compared with Env 459C alone. These data demonstrate that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens capable of eliciting antibody responses with greater neutralization breadth. Cell Press 2019-01-09 /pmc/articles/PMC6331341/ /pubmed/30629920 http://dx.doi.org/10.1016/j.chom.2018.12.001 Text en © 2018 The Author(s) 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
Bricault, Christine A.
Yusim, Karina
Seaman, Michael S.
Yoon, Hyejin
Theiler, James
Giorgi, Elena E.
Wagh, Kshitij
Theiler, Maxwell
Hraber, Peter
Macke, Jennifer P.
Kreider, Edward F.
Learn, Gerald H.
Hahn, Beatrice H.
Scheid, Johannes F.
Kovacs, James M.
Shields, Jennifer L.
Lavine, Christy L.
Ghantous, Fadi
Rist, Michael
Bayne, Madeleine G.
Neubauer, George H.
McMahan, Katherine
Peng, Hanqin
Chéneau, Coraline
Jones, Jennifer J.
Zeng, Jie
Ochsenbauer, Christina
Nkolola, Joseph P.
Stephenson, Kathryn E.
Chen, Bing
Gnanakaran, S.
Bonsignori, Mattia
Williams, LaTonya D.
Haynes, Barton F.
Doria-Rose, Nicole
Mascola, John R.
Montefiori, David C.
Barouch, Dan H.
Korber, Bette
HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design
title HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design
title_full HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design
title_fullStr HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design
title_full_unstemmed HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design
title_short HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design
title_sort hiv-1 neutralizing antibody signatures and application to epitope-targeted vaccine design
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331341/
https://www.ncbi.nlm.nih.gov/pubmed/30629920
http://dx.doi.org/10.1016/j.chom.2018.12.001
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