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Title: Design and crystal structure of a native-like HIV-1 envelope trimer that engages multiple broadly neutralizing antibody precursors in vivo

Abstract

Induction of broadly neutralizing antibodies (bNAbs) by HIV-1 envelope glycoprotein immunogens would be a major advance toward an effective vaccine. A critical step in this process is the activation of naive B cells expressing germline (gl) antibody precursors that have the potential to evolve into bNAbs. Here, we reengineered the BG505 SOSIP.664 glycoprotein to engage gl precursors of bNAbs that target either the trimer apex or the CD4-binding site. The resulting BG505 SOSIP.v4.1-GT1 trimer binds multiple bNAb gl precursors in vitro. Immunization experiments in knock-in mice expressing gl-VRC01 or gl-PGT121 show that this trimer activates B cells in vivo, resulting in the secretion of specific antibodies into the sera. A crystal structure of the gl-targeting trimer at 3.2-Å resolution in complex with neutralizing antibodies 35O22 and 9H+109L reveals a native-like conformation and the successful incorporation of design features associated with binding of multiple gl-bNAb precursors.

Authors:
ORCiD logo [1];  [2];  [3]; ORCiD logo [4];  [1];  [1]; ORCiD logo [5]; ORCiD logo [6]; ORCiD logo [7]; ORCiD logo [2];  [8];  [3];  [2];  [2];  [3];  [6];  [1]; ORCiD logo [6];  [1]; ORCiD logo [4] more »; ORCiD logo [9];  [1];  [7]; ORCiD logo [2];  [7];  [2];  [5]; ORCiD logo [6]; ORCiD logo [6]; ORCiD logo [4]; ORCiD logo [10];  [2];  [11] « less
  1. Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
  2. Department of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA
  3. Laboratory of Molecular Immunology, The Rockefeller University, New York, NY
  4. Department of Immunology and Microbiology, Scripps CHAVI-ID, The Scripps Research Institute, La Jolla, CA
  5. Seattle Biomedical Research Institute, Seattle, WA
  6. Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY
  7. Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford, England, UK
  8. Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands, Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
  9. Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
  10. Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, Howard Hughes Medical Institute, The Rockefeller University, New York, NY
  11. Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands, Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
1377638
Grant/Contract Number:  
AC02-06CH11357
Resource Type:
Published Article
Journal Name:
Journal of Experimental Medicine
Additional Journal Information:
Journal Name: Journal of Experimental Medicine Journal Volume: 214 Journal Issue: 9; Journal ID: ISSN 0022-1007
Publisher:
Rockefeller University Press
Country of Publication:
United States
Language:
English

Citation Formats

Medina-Ramírez, Max, Garces, Fernando, Escolano, Amelia, Skog, Patrick, de Taeye, Steven W., Del Moral-Sanchez, Ivan, McGuire, Andrew T., Yasmeen, Anila, Behrens, Anna-Janina, Ozorowski, Gabriel, van den Kerkhof, Tom L. G. M., Freund, Natalia T., Dosenovic, Pia, Hua, Yuanzi, Gitlin, Alexander D., Cupo, Albert, van der Woude, Patricia, Golabek, Michael, Sliepen, Kwinten, Blane, Tanya, Kootstra, Neeltje, van Breemen, Mariëlle J., Pritchard, Laura K., Stanfield, Robyn L., Crispin, Max, Ward, Andrew B., Stamatatos, Leonidas, Klasse, Per Johan, Moore, John P., Nemazee, David, Nussenzweig, Michel C., Wilson, Ian A., and Sanders, Rogier W. Design and crystal structure of a native-like HIV-1 envelope trimer that engages multiple broadly neutralizing antibody precursors in vivo. United States: N. p., 2017. Web. doi:10.1084/jem.20161160.
Medina-Ramírez, Max, Garces, Fernando, Escolano, Amelia, Skog, Patrick, de Taeye, Steven W., Del Moral-Sanchez, Ivan, McGuire, Andrew T., Yasmeen, Anila, Behrens, Anna-Janina, Ozorowski, Gabriel, van den Kerkhof, Tom L. G. M., Freund, Natalia T., Dosenovic, Pia, Hua, Yuanzi, Gitlin, Alexander D., Cupo, Albert, van der Woude, Patricia, Golabek, Michael, Sliepen, Kwinten, Blane, Tanya, Kootstra, Neeltje, van Breemen, Mariëlle J., Pritchard, Laura K., Stanfield, Robyn L., Crispin, Max, Ward, Andrew B., Stamatatos, Leonidas, Klasse, Per Johan, Moore, John P., Nemazee, David, Nussenzweig, Michel C., Wilson, Ian A., & Sanders, Rogier W. Design and crystal structure of a native-like HIV-1 envelope trimer that engages multiple broadly neutralizing antibody precursors in vivo. United States. doi:10.1084/jem.20161160.
Medina-Ramírez, Max, Garces, Fernando, Escolano, Amelia, Skog, Patrick, de Taeye, Steven W., Del Moral-Sanchez, Ivan, McGuire, Andrew T., Yasmeen, Anila, Behrens, Anna-Janina, Ozorowski, Gabriel, van den Kerkhof, Tom L. G. M., Freund, Natalia T., Dosenovic, Pia, Hua, Yuanzi, Gitlin, Alexander D., Cupo, Albert, van der Woude, Patricia, Golabek, Michael, Sliepen, Kwinten, Blane, Tanya, Kootstra, Neeltje, van Breemen, Mariëlle J., Pritchard, Laura K., Stanfield, Robyn L., Crispin, Max, Ward, Andrew B., Stamatatos, Leonidas, Klasse, Per Johan, Moore, John P., Nemazee, David, Nussenzweig, Michel C., Wilson, Ian A., and Sanders, Rogier W. Mon . "Design and crystal structure of a native-like HIV-1 envelope trimer that engages multiple broadly neutralizing antibody precursors in vivo". United States. doi:10.1084/jem.20161160.
@article{osti_1377638,
title = {Design and crystal structure of a native-like HIV-1 envelope trimer that engages multiple broadly neutralizing antibody precursors in vivo},
author = {Medina-Ramírez, Max and Garces, Fernando and Escolano, Amelia and Skog, Patrick and de Taeye, Steven W. and Del Moral-Sanchez, Ivan and McGuire, Andrew T. and Yasmeen, Anila and Behrens, Anna-Janina and Ozorowski, Gabriel and van den Kerkhof, Tom L. G. M. and Freund, Natalia T. and Dosenovic, Pia and Hua, Yuanzi and Gitlin, Alexander D. and Cupo, Albert and van der Woude, Patricia and Golabek, Michael and Sliepen, Kwinten and Blane, Tanya and Kootstra, Neeltje and van Breemen, Mariëlle J. and Pritchard, Laura K. and Stanfield, Robyn L. and Crispin, Max and Ward, Andrew B. and Stamatatos, Leonidas and Klasse, Per Johan and Moore, John P. and Nemazee, David and Nussenzweig, Michel C. and Wilson, Ian A. and Sanders, Rogier W.},
abstractNote = {Induction of broadly neutralizing antibodies (bNAbs) by HIV-1 envelope glycoprotein immunogens would be a major advance toward an effective vaccine. A critical step in this process is the activation of naive B cells expressing germline (gl) antibody precursors that have the potential to evolve into bNAbs. Here, we reengineered the BG505 SOSIP.664 glycoprotein to engage gl precursors of bNAbs that target either the trimer apex or the CD4-binding site. The resulting BG505 SOSIP.v4.1-GT1 trimer binds multiple bNAb gl precursors in vitro. Immunization experiments in knock-in mice expressing gl-VRC01 or gl-PGT121 show that this trimer activates B cells in vivo, resulting in the secretion of specific antibodies into the sera. A crystal structure of the gl-targeting trimer at 3.2-Å resolution in complex with neutralizing antibodies 35O22 and 9H+109L reveals a native-like conformation and the successful incorporation of design features associated with binding of multiple gl-bNAb precursors.},
doi = {10.1084/jem.20161160},
journal = {Journal of Experimental Medicine},
number = 9,
volume = 214,
place = {United States},
year = {2017},
month = {8}
}

Journal Article:
Free Publicly Available Full Text
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DOI: 10.1084/jem.20161160

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Works referenced in this record:

Affinity Maturation of a Potent Family of HIV Antibodies Is Primarily Focused on Accommodating or Avoiding Glycans
journal, December 2015


Structure and immune recognition of trimeric pre-fusion HIV-1 Env
journal, October 2014

  • Pancera, Marie; Zhou, Tongqing; Druz, Aliaksandr
  • Nature, Vol. 514, Issue 7523
  • DOI: 10.1038/nature13808

On the use of the merging R factor as a quality indicator for X-ray data
journal, April 1997


Immunization for HIV-1 Broadly Neutralizing Antibodies in Human Ig Knockin Mice
journal, June 2015


Natively glycosylated HIV-1 Env structure reveals new mode for antibody recognition of the CD4-binding site
journal, September 2016

  • Gristick, Harry B.; von Boehmer, Lotta; West Jr, Anthony P.
  • Nature Structural & Molecular Biology, Vol. 23, Issue 10
  • DOI: 10.1038/nsmb.3291

Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9
journal, November 2011

  • McLellan, Jason S.; Pancera, Marie; Carrico, Chris
  • Nature, Vol. 480, Issue 7377
  • DOI: 10.1038/nature10696

Native-like Env trimers as a platform for HIV-1 vaccine design
journal, January 2017

  • Sanders, Rogier W.; Moore, John P.
  • Immunological Reviews, Vol. 275, Issue 1
  • DOI: 10.1111/imr.12481

Structural basis for HIV-1 gp120 recognition by a germ-line version of a broadly neutralizing antibody
journal, March 2013

  • Scharf, L.; West, A. P.; Gao, H.
  • Proceedings of the National Academy of Sciences, Vol. 110, Issue 15
  • DOI: 10.1073/pnas.1303682110

Affinity maturation in an HIV broadly neutralizing B-cell lineage through reorientation of variable domains
journal, June 2014

  • Fera, D.; Schmidt, A. G.; Haynes, B. F.
  • Proceedings of the National Academy of Sciences, Vol. 111, Issue 28
  • DOI: 10.1073/pnas.1409954111

Broad neutralization coverage of HIV by multiple highly potent antibodies
journal, September 2011

  • Walker, Laura M.; Huber, Michael; Doores, Katie J.
  • Nature, Vol. 477, Issue 7365
  • DOI: 10.1038/nature10373

Contrasting IgG Structures Reveal Extreme Asymmetry and Flexibility
journal, May 2002

  • Saphire, Erica Ollmann; Stanfield, Robyn L.; Max Crispin, M. D.
  • Journal of Molecular Biology, Vol. 319, Issue 1
  • DOI: 10.1016/S0022-2836(02)00244-9

HIV-1 neutralizing antibodies: understanding nature's pathways
journal, June 2013

  • Mascola, John R.; Haynes, Barton F.
  • Immunological Reviews, Vol. 254, Issue 1
  • DOI: 10.1111/imr.12075

Maturation Pathways of Cross-Reactive HIV-1 Neutralizing Antibodies
journal, November 2009

  • Xiao, Xiaodong; Chen, Weizao; Feng, Yang
  • Viruses, Vol. 1, Issue 3
  • DOI: 10.3390/v1030802

Effective, low-titer antibody protection against low-dose repeated mucosal SHIV challenge in macaques
journal, June 2009

  • Hessell, Ann J.; Poignard, Pascal; Hunter, Meredith
  • Nature Medicine, Vol. 15, Issue 8
  • DOI: 10.1038/nm.1974

Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 Binding
journal, July 2011


Specifically modified Env immunogens activate B-cell precursors of broadly neutralizing HIV-1 antibodies in transgenic mice
journal, February 2016

  • McGuire, Andrew T.; Gray, Matthew D.; Dosenovic, Pia
  • Nature Communications, Vol. 7, Issue 1
  • DOI: 10.1038/ncomms10618

Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals
journal, March 2009

  • Scheid, Johannes F.; Mouquet, Hugo; Feldhahn, Niklas
  • Nature, Vol. 458, Issue 7238
  • DOI: 10.1038/nature07930

Stabilized HIV-1 envelope glycoprotein trimers for vaccine use
journal, January 2017

  • Medina-Ramírez, Max; Sanders, Rogier W.; Sattentau, Quentin J.
  • Current Opinion in HIV and AIDS, Vol. 12, Issue 3
  • DOI: 10.1097/COH.0000000000000363

A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but Not Non-Neutralizing Antibodies
journal, September 2013


Antibody-virus co-evolution in HIV infection: paths for HIV vaccine development
journal, January 2017

  • Bonsignori, Mattia; Liao, Hua-Xin; Gao, Feng
  • Immunological Reviews, Vol. 275, Issue 1
  • DOI: 10.1111/imr.12509

Crystal Structure of a Soluble Cleaved HIV-1 Envelope Trimer
journal, October 2013


Receptor Editing in a Transgenic Mouse Model: Site, Efficiency, and Role in B Cell Tolerance and Antibody Diversification
journal, December 1997


Rational HIV Immunogen Design to Target Specific Germline B Cell Receptors
journal, March 2013


Chemical Synthesis of Highly Congested gp120 V1V2 N -Glycopeptide Antigens for Potential HIV-1-Directed Vaccines
journal, August 2013

  • Aussedat, Baptiste; Vohra, Yusuf; Park, Peter K.
  • Journal of the American Chemical Society, Vol. 135, Issue 35
  • DOI: 10.1021/ja405990z

Structural basis for germline antibody recognition of HIV-1 immunogens
journal, March 2016


Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex
journal, November 2014

  • Sok, Devin; van Gils, Marit J.; Pauthner, Matthias
  • Proceedings of the National Academy of Sciences, Vol. 111, Issue 49
  • DOI: 10.1073/pnas.1415789111

Structures of HIV-1 Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design
journal, December 2015

  • Gorman, Jason; Soto, Cinque; Yang, Max M.
  • Nature Structural & Molecular Biology, Vol. 23, Issue 1
  • DOI: 10.1038/nsmb.3144

HIV-1 Fitness Cost Associated with Escape from the VRC01 Class of CD4 Binding Site Neutralizing Antibodies
journal, January 2015

  • Lynch, Rebecca M.; Wong, Patrick; Tran, Lillian
  • Journal of Virology, Vol. 89, Issue 8
  • DOI: 10.1128/JVI.03608-14

Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus
journal, April 2013

  • Liao, Hua-Xin; Lynch, Rebecca; Zhou, Tongqing
  • Nature, Vol. 496, Issue 7446
  • DOI: 10.1038/nature12053

HIV-1 Envelope Trimer Design and Immunization Strategies To Induce Broadly Neutralizing Antibodies
journal, March 2016

  • de Taeye, Steven W.; Moore, John P.; Sanders, Rogier W.
  • Trends in Immunology, Vol. 37, Issue 3
  • DOI: 10.1016/j.it.2016.01.007

Few and Far Between: How HIV May Be Evading Antibody Avidity
journal, May 2010


Progress toward active or passive HIV-1 vaccination
journal, December 2016

  • Escolano, Amelia; Dosenovic, Pia; Nussenzweig, Michel C.
  • The Journal of Experimental Medicine, Vol. 214, Issue 1
  • DOI: 10.1084/jem.20161765

Thermodynamic Analysis of the Binding of 2F5 (Fab and Immunoglobulin G Forms) to Its gp41 Epitope Reveals a Strong Influence of the Immunoglobulin Fc Region on Affinity
journal, December 2013

  • Crespillo, Sara; Casares, Salvador; Mateo, Pedro L.
  • Journal of Biological Chemistry, Vol. 289, Issue 2
  • DOI: 10.1074/jbc.C113.524439

HIV-1 neutralizing antibodies induced by native-like envelope trimers
journal, June 2015


The HIV-1 envelope glycoprotein structure: nailing down a moving target
journal, January 2017

  • Ward, Andrew B.; Wilson, Ian A.
  • Immunological Reviews, Vol. 275, Issue 1
  • DOI: 10.1111/imr.12507

Human Ig knockin mice to study the development and regulation of HIV-1 broadly neutralizing antibodies
journal, January 2017

  • Verkoczy, Laurent; Alt, Frederick W.; Tian, Ming
  • Immunological Reviews, Vol. 275, Issue 1
  • DOI: 10.1111/imr.12505

Antibody responses to envelope glycoproteins in HIV-1 infection
journal, May 2015

  • Burton, Dennis R.; Mascola, John R.
  • Nature Immunology, Vol. 16, Issue 6
  • DOI: 10.1038/ni.3158

Sulfation, the Up-and-Coming Post-Translational Modification:  Its Role and Mechanism in Protein−Protein Interaction
journal, March 2007

  • Woods, Amina S.; Wang, Hay-Yan J.; Jackson, Shelley N.
  • Journal of Proteome Research, Vol. 6, Issue 3
  • DOI: 10.1021/pr060529g

HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen
journal, March 2016


Induction of HIV Neutralizing Antibody Lineages in Mice with Diverse Precursor Repertoires
journal, September 2016


Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01
journal, July 2010


Priming HIV-1 broadly neutralizing antibody precursors in human Ig loci transgenic mice
journal, September 2016


The carbohydrate at asparagine 386 on HIV-1 gp120 is not essential for protein folding and function but is involved in immune evasion
journal, January 2008

  • Sanders, Rogier W.; van Anken, Eelco; Nabatov, Alexei A.
  • Retrovirology, Vol. 5, Issue 1
  • DOI: 10.1186/1742-4690-5-10

Sequential and Simultaneous Immunization of Rabbits with HIV-1 Envelope Glycoprotein SOSIP.664 Trimers from Clades A, B and C
journal, September 2016


Neutralization Escape Variants of Human Immunodeficiency Virus Type 1 Are Transmitted from Mother to Infant
journal, December 2005


Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein
journal, March 2016


MolProbity : all-atom structure validation for macromolecular crystallography
journal, December 2009

  • Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1
  • DOI: 10.1107/S0907444909042073

Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-neutralizing Epitopes
journal, December 2015

  • de Taeye, Steven W.; Ozorowski, Gabriel; Torrents de la Peña, Alba
  • Cell, Vol. 163, Issue 7
  • DOI: 10.1016/j.cell.2015.11.056

Coot model-building tools for molecular graphics
journal, November 2004

  • Emsley, Paul; Cowtan, Kevin
  • Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132
  • DOI: 10.1107/S0907444904019158

Subtypes of Human Immunodeficiency Virus Type 1 and Disease Stage among Women in Nairobi, Kenya
journal, January 1999


Broad and Potent Neutralizing Antibodies from an African Donor Reveal a New HIV-1 Vaccine Target
journal, September 2009


Binding of inferred germline precursors of broadly neutralizing HIV-1 antibodies to native-like envelope trimers
journal, December 2015


Role of antigen receptor affinity in T cell–independent antibody responses in vivo
journal, March 2002

  • Shih, Tien-An Yang; Roederer, Mario; Nussenzweig, Michel C.
  • Nature Immunology, Vol. 3, Issue 4
  • DOI: 10.1038/ni776

Engineering HIV envelope protein to activate germline B cell receptors of broadly neutralizing anti-CD4 binding site antibodies
journal, March 2013

  • McGuire, Andrew T.; Hoot, Sam; Dreyer, Anita M.
  • The Journal of Experimental Medicine, Vol. 210, Issue 4
  • DOI: 10.1084/jem.20122824

A Native-Like SOSIP.664 Trimer Based on an HIV-1 Subtype B env Gene
journal, January 2015

  • Pugach, Pavel; Ozorowski, Gabriel; Cupo, Albert
  • Journal of Virology, Vol. 89, Issue 6
  • DOI: 10.1128/JVI.03473-14

Mechanism of Neutralization by the Broadly Neutralizing HIV-1 Monoclonal Antibody VRC01
journal, June 2011

  • Li, Y.; O'Dell, S.; Walker, L. M.
  • Journal of Virology, Vol. 85, Issue 17
  • DOI: 10.1128/JVI.00754-11

PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010

  • Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
  • DOI: 10.1107/S0907444909052925

Sequential Immunization Elicits Broadly Neutralizing Anti-HIV-1 Antibodies in Ig Knockin Mice
journal, September 2016


Antibodies in HIV-1 Vaccine Development and Therapy
journal, September 2013


Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer
journal, March 2015


Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys
journal, October 2013

  • Barouch, Dan H.; Whitney, James B.; Moldt, Brian
  • Nature, Vol. 503, Issue 7475
  • DOI: 10.1038/nature12744

Cross‐Reactive Neutralizing Humoral Immunity Does Not Protect from HIV Type 1 Disease Progression
journal, April 2010

  • Euler, Zelda; van Gils, Marit J.; Bunnik, Evelien M.
  • The Journal of Infectious Diseases, Vol. 201, Issue 7
  • DOI: 10.1086/651144

Anti-HIV B Cell Lines as Candidate Vaccine Biosensors
journal, October 2012

  • Ota, Takayuki; Doyle-Cooper, Colleen; Cooper, Anthony B.
  • The Journal of Immunology, Vol. 189, Issue 10
  • DOI: 10.4049/jimmunol.1202165

Structural Evolution of Glycan Recognition by a Family of Potent HIV Antibodies
journal, September 2014


Somatic Mutations of the Immunoglobulin Framework Are Generally Required for Broad and Potent HIV-1 Neutralization
journal, March 2013


Passive transfer of modest titers of potent and broadly neutralizing anti-HIV monoclonal antibodies block SHIV infection in macaques
journal, August 2014

  • Shingai, Masashi; Donau, Olivia K.; Plishka, Ronald J.
  • The Journal of Experimental Medicine, Vol. 211, Issue 10
  • DOI: 10.1084/jem.20132494

B-cell–lineage immunogen design in vaccine development with HIV-1 as a case study
journal, May 2012

  • Haynes, Barton F.; Kelsoe, Garnett; Harrison, Stephen C.
  • Nature Biotechnology, Vol. 30, Issue 5
  • DOI: 10.1038/nbt.2197

Structural basis for germ-line gene usage of a potent class of antibodies targeting the CD4-binding site of HIV-1 gp120
journal, June 2012

  • West, Anthony P.; Diskin, Ron; Nussenzweig, Michel C.
  • Proceedings of the National Academy of Sciences, Vol. 109, Issue 30
  • DOI: 10.1073/pnas.1208984109

Identification of Common Features in Prototype Broadly Neutralizing Antibodies to HIV Envelope V2 Apex to Facilitate Vaccine Design
journal, November 2015


Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies
journal, March 2014

  • Doria-Rose, Nicole A.; Schramm, Chaim A.; Gorman, Jason
  • Nature, Vol. 509, Issue 7498
  • DOI: 10.1038/nature13036

Prevalence of broadly neutralizing antibody responses during chronic HIV-1 infection
journal, January 2014


Outer Domain of HIV-1 gp120: Antigenic Optimization, Structural Malleability, and Crystal Structure with Antibody VRC-PG04
journal, December 2012

  • Joyce, M. G.; Kanekiyo, M.; Xu, L.
  • Journal of Virology, Vol. 87, Issue 4
  • DOI: 10.1128/JVI.02717-12

A single injection of anti-HIV-1 antibodies protects against repeated SHIV challenges
journal, April 2016

  • Gautam, Rajeev; Nishimura, Yoshiaki; Pegu, Amarendra
  • Nature, Vol. 533, Issue 7601
  • DOI: 10.1038/nature17677

Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing
journal, August 2011


Germline-targeting immunogens
journal, January 2017

  • Stamatatos, Leonidas; Pancera, Marie; McGuire, Andrew T.
  • Immunological Reviews, Vol. 275, Issue 1
  • DOI: 10.1111/imr.12483

Polyreactivity increases the apparent affinity of anti-HIV antibodies by heteroligation
journal, September 2010

  • Mouquet, Hugo; Scheid, Johannes F.; Zoller, Markus J.
  • Nature, Vol. 467, Issue 7315
  • DOI: 10.1038/nature09385

HIV Vaccine Design to Target Germline Precursors of Glycan-Dependent Broadly Neutralizing Antibodies
journal, September 2016


Binding of autoreactive mouse anti-type II collagen antibodies derived from the primary and the secondary immune response investigated with the biosensor technique
journal, December 1995


Priming a broadly neutralizing antibody response to HIV-1 using a germline-targeting immunogen
journal, June 2015


[20] Processing of X-ray diffraction data collected in oscillation mode
book, January 1997


HIV-1 envelope glycoprotein signatures that correlate with the development of cross-reactive neutralizing activity
journal, January 2013

  • van den Kerkhof, Tom L. G. M.; Feenstra, K.; Euler, Zelda
  • Retrovirology, Vol. 10, Issue 1
  • DOI: 10.1186/1742-4690-10-102

Structural Constraints Determine the Glycosylation of HIV-1 Envelope Trimers
journal, June 2015


Broadly neutralizing antibodies against HIV-1: Templates for a vaccine
journal, January 2013


Structural Basis of Immune Evasion at the Site of CD4 Attachment on HIV-1 gp120
journal, November 2009