Overcoming Steric Restrictions of VRC01 HIV-1 Neutralizing Antibodies through Immunization

Parks, K. Rachael; MacCamy, Anna J.; Trichka, Josephine; Gray, Matthew; Weidle, Connor; Borst, Andrew J.; Khechaduri, Arineh; Takushi, Brittany; Agrawal, Parul; Guenaga, Javier; Wyatt, Richard T.; Coler, Rhea; Seaman, Michael; LaBranche, Celia; Montefiori, David C.; Veesler, David; Pancera, Marie; McGuire, Andrew; Stamatatos, Leonidas

doi:10.1016/j.celrep.2019.10.071

Title: Overcoming Steric Restrictions of VRC01 HIV-1 Neutralizing Antibodies through Immunization

Abstract

Broadly HIV-1 neutralizing VRC01 class antibodies target the CD4-binding site of Env. They are derived from VH1-2*02 antibody heavy chains paired with rare light chains expressing 5-amino acid-long CDRL3s. They have been isolated from infected subjects but have not yet been elicited by immunization. Env-derived immunogens capable of binding the germline forms of VRC01 B cell receptors on naive B cells have been designed and evaluated in knockin mice. However, the elicited antibodies cannot bypass glycans present on the conserved position N276 of Env, which restricts access to the CD4-binding site. Efforts to guide the appropriate maturation of these antibodies by sequential immunization have not yet been successful. Here, we report on a two-step immunization scheme that leads to the maturation of VRC01-like antibodies capable of accommodating the N276 glycan and displaying autologous tier 2 neutralizing activities. Our results are relevant to clinical trials aiming to elicit VRC01 antibodies.

Authors:

Parks, K. Rachael ^[1]; MacCamy, Anna J. ^[2]; Trichka, Josephine ^[2]; Gray, Matthew ^[2]; Weidle, Connor ^[2]; Borst, Andrew J. ^[3]; Khechaduri, Arineh ^[2]; Takushi, Brittany ^[2]; Agrawal, Parul ^[2]; Guenaga, Javier ^[4]; Wyatt, Richard T. ^[4]; Coler, Rhea ^[5]; Seaman, Michael ^[6]; LaBranche, Celia ^[7]; Montefiori, David C. ^[7]; Veesler, David ^[3]; Pancera, Marie ^[8]; McGuire, Andrew ^[1]; Stamatatos, Leonidas ^[1]

Vaccines and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Global Health, University of Washington, Seattle, WA, USA
Vaccines and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Department of Biochemistry, University of Washington, Seattle, WA, USA
IAVI Neutralizing Antibody Center, Department of Immunology and Microbiology, The Scripps Research Institute, San Diego, CA, USA
Department of Global Health, University of Washington, Seattle, WA, USA; Infectious Disease Research Institute, Seattle, WA, USA
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Laboratory for AIDS Vaccine Research and Development, Duke University, Durham, NC, USA
Vaccines and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA

Publication Date:: Sun Dec 01 00:00:00 EST 2019

Research Org.:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Org.:: USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH); Pew Charitable Trust; Burroughs Wellcome Fund; Arnold and Mabel Beckman Cryo-EM Center; J.B. Pendleton Charitable Trust

OSTI Identifier:: 1623651

Grant/Contract Number:: AC02-05CH11231; R01 AI104384; P01 AI138212; U19 AI109632; HHSN272201800004C; R01GM120553

Resource Type:: Accepted Manuscript

Journal Name:: Cell Reports

Additional Journal Information:: Journal Volume: 29; Journal Issue: 10; Journal ID: ISSN 2211-1247

Publisher:: Elsevier

Country of Publication:: United States

Language:: English

Subject:: 59 BASIC BIOLOGICAL SCIENCES; Cell Biology

Citation Formats


                    Parks, K. Rachael, MacCamy, Anna J., Trichka, Josephine, Gray, Matthew, Weidle, Connor, Borst, Andrew J., Khechaduri, Arineh, Takushi, Brittany, Agrawal, Parul, Guenaga, Javier, Wyatt, Richard T., Coler, Rhea, Seaman, Michael, LaBranche, Celia, Montefiori, David C., Veesler, David, Pancera, Marie, McGuire, Andrew, and Stamatatos, Leonidas. Overcoming Steric Restrictions of VRC01 HIV-1 Neutralizing Antibodies through Immunization.  United States: N. p., 2019. 
Web.  doi:10.1016/j.celrep.2019.10.071.

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                    Parks, K. Rachael, MacCamy, Anna J., Trichka, Josephine, Gray, Matthew, Weidle, Connor, Borst, Andrew J., Khechaduri, Arineh, Takushi, Brittany, Agrawal, Parul, Guenaga, Javier, Wyatt, Richard T., Coler, Rhea, Seaman, Michael, LaBranche, Celia, Montefiori, David C., Veesler, David, Pancera, Marie, McGuire, Andrew, & Stamatatos, Leonidas. Overcoming Steric Restrictions of VRC01 HIV-1 Neutralizing Antibodies through Immunization.  United States.  https://doi.org/10.1016/j.celrep.2019.10.071

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                    Parks, K. Rachael, MacCamy, Anna J., Trichka, Josephine, Gray, Matthew, Weidle, Connor, Borst, Andrew J., Khechaduri, Arineh, Takushi, Brittany, Agrawal, Parul, Guenaga, Javier, Wyatt, Richard T., Coler, Rhea, Seaman, Michael, LaBranche, Celia, Montefiori, David C., Veesler, David, Pancera, Marie, McGuire, Andrew, and Stamatatos, Leonidas. Sun .  
"Overcoming Steric Restrictions of VRC01 HIV-1 Neutralizing Antibodies through Immunization".  United States.  https://doi.org/10.1016/j.celrep.2019.10.071.  https://www.osti.gov/servlets/purl/1623651.

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@article{osti_1623651,

  title        = {Overcoming Steric Restrictions of VRC01 HIV-1 Neutralizing Antibodies through Immunization},

  author       = {Parks, K. Rachael and MacCamy, Anna J. and Trichka, Josephine and Gray, Matthew and Weidle, Connor and Borst, Andrew J. and Khechaduri, Arineh and Takushi, Brittany and Agrawal, Parul and Guenaga, Javier and Wyatt, Richard T. and Coler, Rhea and Seaman, Michael and LaBranche, Celia and Montefiori, David C. and Veesler, David and Pancera, Marie and McGuire, Andrew and Stamatatos, Leonidas},

  abstractNote = {Broadly HIV-1 neutralizing VRC01 class antibodies target the CD4-binding site of Env. They are derived from VH1-2*02 antibody heavy chains paired with rare light chains expressing 5-amino acid-long CDRL3s. They have been isolated from infected subjects but have not yet been elicited by immunization. Env-derived immunogens capable of binding the germline forms of VRC01 B cell receptors on naive B cells have been designed and evaluated in knockin mice. However, the elicited antibodies cannot bypass glycans present on the conserved position N276 of Env, which restricts access to the CD4-binding site. Efforts to guide the appropriate maturation of these antibodies by sequential immunization have not yet been successful. Here, we report on a two-step immunization scheme that leads to the maturation of VRC01-like antibodies capable of accommodating the N276 glycan and displaying autologous tier 2 neutralizing activities. Our results are relevant to clinical trials aiming to elicit VRC01 antibodies.},

  doi          = {10.1016/j.celrep.2019.10.071},

  journal      = {Cell Reports},

  number       = 10,

  volume       = 29,

  place        = {United States},

  year         = {Sun Dec 01 00:00:00 EST 2019},

  month        = {Sun Dec 01 00:00:00 EST 2019}

}

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Title: Overcoming Steric Restrictions of VRC01 HIV-1 Neutralizing Antibodies through Immunization

Abstract

Citation Formats

Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design journal, May 2016

Automated molecular microscopy: The new Leginon system journal, July 2005

Accurate determination of local defocus and specimen tilt in electron microscopy journal, June 2003

Cloning and expression of murine Ig genes from single B cells journal, October 2009

To EBV or not to EBV: Rational vaccine design for a common infection journal, May 2018

Unambiguous Phosphosite Localization using Electron-Transfer/Higher-Energy Collision Dissociation (EThcD) journal, February 2013

DoG Picker and TiltPicker: Software tools to facilitate particle selection in single particle electron microscopy journal, May 2009

Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies journal, May 2013

A Bayesian view on cryo-EM structure determination conference, May 2012

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

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

Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody journal, April 2016

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

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

Expanding the breadth of an HIV-1 vaccine journal, December 2014

Appion: An integrated, database-driven pipeline to facilitate EM image processing journal, April 2009

RELION: Implementation of a Bayesian approach to cryo-EM structure determination journal, December 2012

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

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

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

IMGT/V-QUEST: IMGT Standardized Analysis of the Immunoglobulin (IG) and T Cell Receptor (TR) Nucleotide Sequences journal, June 2011

Soluble Prefusion Closed DS-SOSIP.664-Env Trimers of Diverse HIV-1 Strains journal, December 2017

Single-particle EM reveals plasticity of interactions between the adenovirus penton base and integrin V 3 journal, June 2014

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

Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques journal, May 2019

The human naive B cell repertoire contains distinct subclasses for a germline-targeting HIV-1 vaccine immunogen journal, July 2018

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

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

Arranged Sevenfold: Structural Insights into the C-Terminal Oligomerization Domain of Human C4b-Binding Protein journal, April 2013

In-depth determination and analysis of the human paired heavy- and light-chain antibody repertoire journal, December 2014

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

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

The Oligomerization Domain of C4-Binding Protein (C4bp) Acts as an Adjuvant, and the Fusion Protein Comprised of the 19-Kilodalton Merozoite Surface Protein 1 Fused with the Murine C4bp Domain Protects Mice against Malaria journal, May 2008

A New Glycan-Dependent CD4-Binding Site Neutralizing Antibody Exerts Pressure on HIV-1 In Vivo journal, October 2015

Precursor Frequency and Affinity Determine B Cell Competitive Fitness in Germinal Centers, Tested with Germline-Targeting HIV Vaccine Immunogens journal, January 2018

Teaching a Clone to Walk, One Step at a Time journal, September 2016

IMGT/V-QUEST: the highly customized and integrated system for IG and TR standardized V-J and V-D-J sequence analysis journal, May 2008

Rapid and Focused Maturation of a VRC01-Class HIV Broadly Neutralizing Antibody Lineage Involves Both Binding and Accommodation of the N276-Glycan journal, July 2019

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

Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors journal, June 2015

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

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

HIV-1 Vaccines Based on Antibody Identification, B Cell Ontogeny, and Epitope Structure journal, May 2018

Repertoire comparison of the B-cell receptor-encoding loci in humans and rhesus macaques by next-generation sequencing journal, July 2016

Recombinant HIV Envelope Proteins Fail to Engage Germline Versions of Anti-CD4bs bNAbs journal, January 2013

Anti–HIV-1 B cell responses are dependent on B cell precursor frequency and antigen-binding affinity journal, April 2018

Precursor Frequency and Affinity Determine B Cell Competitive Fitness in Germinal Centers, Tested with Germline-Targeting HIV Vaccine Immunogens journal, January 2018

Recent developments in the PHENIX software for automated crystallographic structure determination journal, November 2003

High-Resolution Description of Antibody Heavy-Chain Repertoires in Humans journal, August 2011

Vectored immunoprophylaxis protects humanized mice from mucosal HIV transmission journal, February 2014

Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody journal, April 2016

Inference of the HIV-1 VRC01 Antibody Lineage Unmutated Common Ancestor Reveals Alternative Pathways to Overcome a Key Glycan Barrier journal, December 2018

Tailored Immunogens Direct Affinity Maturation toward HIV Neutralizing Antibodies journal, September 2016

IMGT/V-QUEST: the highly customized and integrated system for IG and TR standardized V-J and V-D-J sequence analysis journal, May 2008

Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design journal, May 2016

In-depth determination and analysis of the human paired heavy- and light-chain antibody repertoire journal, December 2014

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

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

Anti–HIV-1 B cell responses are dependent on B cell precursor frequency and antigen-binding affinity journal, April 2018

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

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

Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques journal, May 2019

Unambiguous Phosphosite Localization using Electron-Transfer/Higher-Energy Collision Dissociation (EThcD) journal, February 2013

A New Glycan-Dependent CD4-Binding Site Neutralizing Antibody Exerts Pressure on HIV-1 In Vivo journal, October 2015

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

Structure-Guided Redesign Increases the Propensity of HIV Env To Generate Highly Stable Soluble Trimers journal, December 2015

The human naive B cell repertoire contains distinct subclasses for a germline-targeting HIV-1 vaccine immunogen journal, July 2018

Arranged Sevenfold: Structural Insights into the C-Terminal Oligomerization Domain of Human C4b-Binding Protein journal, April 2013

Recombinant HIV Envelope Proteins Fail to Engage Germline Versions of Anti-CD4bs bNAbs journal, January 2013

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

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

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

Soluble Prefusion Closed DS-SOSIP.664-Env Trimers of Diverse HIV-1 Strains journal, December 2017

Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies journal, May 2013

Accelerated cryo-EM structure determination with parallelisation using GPUs in RELION-2 journal, November 2016

HIV-1 Vaccines Based on Antibody Identification, B Cell Ontogeny, and Epitope Structure journal, May 2018

HIV-1 envelope glycan modifications that permit neutralization by germline-reverted VRC01-class broadly neutralizing antibodies journal, November 2018

Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design
journal, May 2016

Automated molecular microscopy: The new Leginon system
journal, July 2005

Accurate determination of local defocus and specimen tilt in electron microscopy
journal, June 2003

Cloning and expression of murine Ig genes from single B cells
journal, October 2009

To EBV or not to EBV: Rational vaccine design for a common infection
journal, May 2018

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journal, February 2013

DoG Picker and TiltPicker: Software tools to facilitate particle selection in single particle electron microscopy
journal, May 2009

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journal, May 2013

A Bayesian view on cryo-EM structure determination
conference, May 2012

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

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

Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody
journal, April 2016

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

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

Expanding the breadth of an HIV-1 vaccine
journal, December 2014

Appion: An integrated, database-driven pipeline to facilitate EM image processing
journal, April 2009

RELION: Implementation of a Bayesian approach to cryo-EM structure determination
journal, December 2012

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

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

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

IMGT/V-QUEST: IMGT Standardized Analysis of the Immunoglobulin (IG) and T Cell Receptor (TR) Nucleotide Sequences
journal, June 2011

Soluble Prefusion Closed DS-SOSIP.664-Env Trimers of Diverse HIV-1 Strains
journal, December 2017

Single-particle EM reveals plasticity of interactions between the adenovirus penton base and integrin V 3
journal, June 2014

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

Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques
journal, May 2019

The human naive B cell repertoire contains distinct subclasses for a germline-targeting HIV-1 vaccine immunogen
journal, July 2018

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

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

Arranged Sevenfold: Structural Insights into the C-Terminal Oligomerization Domain of Human C4b-Binding Protein
journal, April 2013

In-depth determination and analysis of the human paired heavy- and light-chain antibody repertoire
journal, December 2014

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

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

The Oligomerization Domain of C4-Binding Protein (C4bp) Acts as an Adjuvant, and the Fusion Protein Comprised of the 19-Kilodalton Merozoite Surface Protein 1 Fused with the Murine C4bp Domain Protects Mice against Malaria
journal, May 2008

A New Glycan-Dependent CD4-Binding Site Neutralizing Antibody Exerts Pressure on HIV-1 In Vivo
journal, October 2015

Precursor Frequency and Affinity Determine B Cell Competitive Fitness in Germinal Centers, Tested with Germline-Targeting HIV Vaccine Immunogens
journal, January 2018

Teaching a Clone to Walk, One Step at a Time
journal, September 2016

IMGT/V-QUEST: the highly customized and integrated system for IG and TR standardized V-J and V-D-J sequence analysis
journal, May 2008

Rapid and Focused Maturation of a VRC01-Class HIV Broadly Neutralizing Antibody Lineage Involves Both Binding and Accommodation of the N276-Glycan
journal, July 2019

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

Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors
journal, June 2015

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

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

HIV-1 Vaccines Based on Antibody Identification, B Cell Ontogeny, and Epitope Structure
journal, May 2018

Repertoire comparison of the B-cell receptor-encoding loci in humans and rhesus macaques by next-generation sequencing
journal, July 2016

Recombinant HIV Envelope Proteins Fail to Engage Germline Versions of Anti-CD4bs bNAbs
journal, January 2013

Anti–HIV-1 B cell responses are dependent on B cell precursor frequency and antigen-binding affinity
journal, April 2018

Precursor Frequency and Affinity Determine B Cell Competitive Fitness in Germinal Centers, Tested with Germline-Targeting HIV Vaccine Immunogens
journal, January 2018

Recent developments in the PHENIX software for automated crystallographic structure determination
journal, November 2003

High-Resolution Description of Antibody Heavy-Chain Repertoires in Humans
journal, August 2011

Vectored immunoprophylaxis protects humanized mice from mucosal HIV transmission
journal, February 2014

Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody
journal, April 2016

Inference of the HIV-1 VRC01 Antibody Lineage Unmutated Common Ancestor Reveals Alternative Pathways to Overcome a Key Glycan Barrier
journal, December 2018

Tailored Immunogens Direct Affinity Maturation toward HIV Neutralizing Antibodies
journal, September 2016

IMGT/V-QUEST: the highly customized and integrated system for IG and TR standardized V-J and V-D-J sequence analysis
journal, May 2008

Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design
journal, May 2016

In-depth determination and analysis of the human paired heavy- and light-chain antibody repertoire
journal, December 2014

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

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

Anti–HIV-1 B cell responses are dependent on B cell precursor frequency and antigen-binding affinity
journal, April 2018

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

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

Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques
journal, May 2019

Unambiguous Phosphosite Localization using Electron-Transfer/Higher-Energy Collision Dissociation (EThcD)
journal, February 2013

A New Glycan-Dependent CD4-Binding Site Neutralizing Antibody Exerts Pressure on HIV-1 In Vivo
journal, October 2015

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

Structure-Guided Redesign Increases the Propensity of HIV Env To Generate Highly Stable Soluble Trimers
journal, December 2015

The human naive B cell repertoire contains distinct subclasses for a germline-targeting HIV-1 vaccine immunogen
journal, July 2018

Arranged Sevenfold: Structural Insights into the C-Terminal Oligomerization Domain of Human C4b-Binding Protein
journal, April 2013

Recombinant HIV Envelope Proteins Fail to Engage Germline Versions of Anti-CD4bs bNAbs
journal, January 2013

Rational HIV Immunogen Design to Target Specific Germline B Cell Receptors
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Soluble Prefusion Closed DS-SOSIP.664-Env Trimers of Diverse HIV-1 Strains
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Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies
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Accelerated cryo-EM structure determination with parallelisation using GPUs in RELION-2
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HIV-1 Vaccines Based on Antibody Identification, B Cell Ontogeny, and Epitope Structure
journal, May 2018

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Appion: An integrated, database-driven pipeline to facilitate EM image processing
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