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Title: HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design

Abstract

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.

Authors:
 [1];  [2];  [1];  [3];  [2];  [2];  [2];  [3];  [3];  [3];  [4];  [4];  [4];  [5];  [6];  [1];  [1];  [1];  [1];  [1] more »;  [1];  [1];  [7];  [1];  [8];  [8];  [1];  [1];  [9];  [6];  [2];  [10];  [11];  [12];  [13];  [13];  [14];  [9];  [2] « less
+ Show Author Affiliations
  1. Beth Israel Deaconness Medical Center, Boston, MA (United States). Center for Virology and Vaccine Research
  2. Los Alamos National Lab. (LANL), Los Alamos, NM (United States); New Mexico Consortium, Los Alamos, NM (United States)
  3. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  4. Univ. of Pennsylvania, Philadelphia, PA (United States). Perelman School of Medicine. Depts. of Medicine and Microbiology
  5. Massachusetts General Hospital, Boston, MA (United States); Harvard Medical School, Boston, MA (United States)
  6. Children's Hospital, Boston, MA (United States). Division of Molecular Medicine; Harvard Medical School, Boston, MA (United States); Univ. of Colorado, Colorado Springs, CO (United States). Depts. of Chemistry and Biochemistry
  7. Children's Hospital, Boston, MA (United States). Division of Molecular Medicine; Harvard Medical School, Boston, MA (United States)
  8. Univ. of Alabama, Birmingham, AL (United States). Dept. of Medicine and CFAR
  9. Beth Israel Deaconness Medical Center, Boston, MA (United States). Center for Virology and Vaccine Research; Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Ragon Inst. of Massachusetts
  10. Duke Univ., Durham, NC (United States). School of Medicine. Duke Human Vaccine Inst.; Duke Univ., Durham, NC (United States). School of Medicine. Dept. of Medicine
  11. Duke Univ., Durham, NC (United States). School of Medicine. Duke Human Vaccine Inst.
  12. Duke Univ., Durham, NC (United States). School of Medicine. Duke Human Vaccine Inst.; Duke Univ., Durham, NC (United States). School of Medicine. Dept. of Medicine; Duke Univ., Durham, NC (United States). School of Immunology
  13. National Inst. of Health (NIH), Bethesda, MD (United States). National Inst. of Allergy and Infectious Disease. Vaccine Research Center
  14. Duke Univ., Durham, NC (United States). School of Medicine. Duke Human Vaccine Inst.; Duke Univ., Durham, NC (United States). School of Medicine. Dept. of Surgery
Publication Date:
Research Org.:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
OSTI Identifier:
1623654
Grant/Contract Number:  
AC52-06NA25396
Resource Type:
Accepted Manuscript
Journal Name:
Cell Host & Microbe
Additional Journal Information:
Journal Volume: 25; Journal Issue: 1; Journal ID: ISSN 1931-3128
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; Microbiology; Parasitology; Virology

Citation Formats

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., and Korber, Bette. HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design. United States: N. p., 2019. Web. doi:10.1016/j.chom.2018.12.001.
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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. United States. https://doi.org/10.1016/j.chom.2018.12.001
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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., and Korber, Bette. Tue . "HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design". United States. https://doi.org/10.1016/j.chom.2018.12.001. https://www.osti.gov/servlets/purl/1623654.
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@article{osti_1623654,
title = {HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design},
author = {Bricault, Christine A. and Yusim, Karina and Seaman, Michael S. and Yoon, Hyejin and Theiler, James and Giorgi, Elena E. and Wagh, Kshitij and Theiler, Maxwell and Hraber, Peter and Macke, Jennifer P. and Kreider, Edward F. and Learn, Gerald H. and Hahn, Beatrice H. and Scheid, Johannes F. and Kovacs, James M. and Shields, Jennifer L. and Lavine, Christy L. and Ghantous, Fadi and Rist, Michael and Bayne, Madeleine G. and Neubauer, George H. and McMahan, Katherine and Peng, Hanqin and Chéneau, Coraline and Jones, Jennifer J. and Zeng, Jie and Ochsenbauer, Christina and Nkolola, Joseph P. and Stephenson, Kathryn E. and Chen, Bing and Gnanakaran, S. and Bonsignori, Mattia and Williams, LaTonya D. and Haynes, Barton F. and Doria-Rose, Nicole and Mascola, John R. and Montefiori, David C. and Barouch, Dan H. and Korber, Bette},
abstractNote = {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.},
doi = {10.1016/j.chom.2018.12.001},
journal = {Cell Host & Microbe},
number = 1,
volume = 25,
place = {United States},
year = {Tue Jan 01 00:00:00 EST 2019},
month = {Tue Jan 01 00:00:00 EST 2019}
}
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    A de novo approach to inferring within-host fitness effects during untreated HIV-1 infection
    text, January 2020

    • Illingworth, Christopher J. R.; Raghwani, Jayna; Serwadda, David
    • Apollo - University of Cambridge Repository
    • DOI: 10.17863/cam.53933
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