Skip to main content
U.S. Department of Energy
Office of Scientific and Technical Information

Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence

Journal Article · · Nature Communications
 [1];  [2];  [3];  [4];  [5];  [6];  [7];  [7];  [7];  [3];  [8];  [9];  [3];  [8];  [8];  [3];  [3];  [3];  [3];  [3] more »;  [3];  [10];  [10];  [11];  [12];  [3];  [13];  [11];  [8];  [4];  [14];  [15];  [16];  [17];  [18] « less
  1. Univ. of Amsterdam (Netherlands). Dept. of Medical Microbiology, Amsterdam Infection & Immunity Institute; DOE/OSTI
  2. The Scripps Research Insttute, La Jolla, CA (United States). Dept. of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD); Seoul National Univ. (Korea, Republic of). Research Institute of Pharmaceutical Sciences, College of Pharmacy
  3. Univ. of Amsterdam (Netherlands). Dept. of Medical Microbiology, Amsterdam Infection & Immunity Institute
  4. Biomedical Primate Research Centre, Rijswijk (Netherlands). Dept. of Virology
  5. The Scripps Research Insttute, La Jolla, CA (United States). Dept. of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD); Amgen Inc., Thousand Oaks, CA (United States). Dept. of Therapeutics Discovery
  6. Univ. of Oxford (United Kingdom). Oxford Glycobiology Institute, Department of Biochemistry; New England Biolabs Inc., Ipswich, MA (United States)
  7. The Scripps Research Insttute, La Jolla, CA (United States). Dept. of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD)
  8. The Scripps Research Insttute, La Jolla, CA (United States). Dept. of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD)
  9. IRCCS San Raffaele Scientific Institute, Milan (Italy). Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and Infectious Diseases
  10. Carlos III Health Inst., Madrid (Spain). AIDS Immunopathology Unit
  11. Duke Univ., Durham, NC (United States). Medical Center, Dept. of Surgery
  12. IRCCS San Raffaele Scientific Institute, Milan (Italy). Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and Infectious Diseases
  13. Univ. of Oxford (United Kingdom). Dept. of Biochemistry, Oxford Glycobiology Institute; Univ. of Southampton (United Kingdom). Centre for Biological Sciences and Inst. for Life Sciences
  14. Cornell Univ., Ithaca, NY (United States). Weill Medical College, Dept. of Microbiology and Immunology
  15. Imperial College, London (United Kingdom). Section of Virology, Division of Infectious Diseases, Dept. of Medicine
  16. Biomedical Primate Research Centre, Rijswijk (Netherlands). Dept. of Virology
  17. The Scripps Research Insttute, La Jolla, CA (United States). Dept. of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD); Scripps Research Institute, San Diego, CA (United States). Skaggs Inst. for Chemical Biology
  18. Univ. of Amsterdam (Netherlands). Dept. of Medical Microbiology, Amsterdam Infection & Immunity Institute; Cornell Univ., Ithaca, NY (United States). Weill Medical College, Dept. of Microbiology and Immunology
Stabilized HIV-1 envelope glycoproteins (Env) that resemble the native Env are utilized in vaccination strategies aimed at inducing broadly neutralizing antibodies (bNAbs). To limit the exposure of rare isolate-specific antigenic residues/determinants we generated a SOSIP trimer based on a consensus sequence of all HIV-1 group M isolates (ConM). The ConM trimer displays the epitopes of most known bNAbs and several germline bNAb precursors. The crystal structure of the ConM trimer at 3.9Å resolution resembles that of the native Env trimer and its antigenic surface displays few rare residues. The ConM trimer elicits strong NAb responses against the autologous virus in rabbits and macaques that are significantly enhanced when it is presented on ferritin nanoparticles. The dominant NAb specificity is directed against an epitope at or close to the trimer apex. Immunogens based on consensus sequences might have utility in engineering vaccines against HIV-1 and other viruses.
Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
Bill and Melinda Gates Foundation; European Research Council (ERC); National Institutes of Health (NIH); National Research Foundation of Korea (NRF); USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1624156
Alternate ID(s):
OSTI ID: 1847725
Journal Information:
Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 10; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English

References (102)

Changes in growth properties on passage in tissue culture of viruses derived from infectious molecular clones of HIV-1LAI, HIV-1MAL, and HIV-1ELI journal December 1991
Structural Evolution of Glycan Recognition by a Family of Potent HIV Antibodies journal September 2014
Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G journal May 2016
Structural Constraints Determine the Glycosylation of HIV-1 Envelope Trimers journal June 2015
Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein journal March 2016
Holes in the Glycan Shield of the Native HIV Envelope Are a Target of Trimer-Elicited Neutralizing Antibodies journal August 2016
A Universal Approach to Optimize the Folding and Stability of Prefusion-Closed HIV-1 Envelope Trimers journal April 2018
Affinity Maturation of a Potent Family of HIV Antibodies Is Primarily Focused on Accommodating or Avoiding Glycans journal December 2015
HIV-1 Envelope Trimer Design and Immunization Strategies To Induce Broadly Neutralizing Antibodies journal March 2016
Nanoparticle vaccines journal January 2014
A group M consensus envelope glycoprotein induces antibodies that neutralize subsets of subtype B and C HIV-1 primary viruses journal September 2006
N-terminal substitutions in HIV-1 gp41 reduce the expression of non-trimeric envelope glycoproteins on the virus journal March 2008
Binding of inferred germline precursors of broadly neutralizing HIV-1 antibodies to native-like envelope trimers journal December 2015
Two-Component Ferritin Nanoparticles for Multimerization of Diverse Trimeric Antigens journal February 2018
Broad and potent HIV-1 neutralization by a human antibody that binds the gp41–gp120 interface journal September 2014
Antibodies to a conformational epitope on gp41 neutralize HIV-1 by destabilizing the Env spike journal September 2015
An HIV-1 antibody from an elite neutralizer implicates the fusion peptide as a site of vulnerability journal November 2016
Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns journal October 2010
Structure of a cleavage-independent HIV Env recapitulates the glycoprotein architecture of the native cleaved trimer journal May 2018
Differential processing of HIV envelope glycans on the virus and soluble recombinant trimer journal September 2018
A consensus-hemagglutinin-based DNA vaccine that protects mice against divergent H5N1 influenza viruses journal September 2008
Design and structure of two HIV-1 clade C SOSIP.664 trimers that increase the arsenal of native-like Env immunogens journal September 2015
Immunosilencing a Highly Immunogenic Protein Trimerization Domain journal January 2015
Dynamic light-scattering analysis of full-length human RPA14/32 dimer: purification, crystallization and self-association journal February 2001
Coot model-building tools for molecular graphics journal November 2004
Solving structures of protein complexes by molecular replacement with Phaser journal December 2006
MolProbity : all-atom structure validation for macromolecular crystallography journal December 2009
REFMAC 5 for the refinement of macromolecular crystal structures journal March 2011
Native-like Env trimers as a platform for HIV-1 vaccine design journal January 2017
The HIV-1 envelope glycoprotein structure: nailing down a moving target journal January 2017
Polyvalent vaccine approaches to combat HIV-1 diversity journal January 2017
Diversity Considerations in HIV-1 Vaccine Selection journal June 2002
Rational HIV Immunogen Design to Target Specific Germline B Cell Receptors journal March 2013
Cryo-EM Structure of a Fully Glycosylated Soluble Cleaved HIV-1 Envelope Trimer journal October 2013
HIV-1 neutralizing antibodies induced by native-like envelope trimers journal June 2015
Cryo-EM structure of a native, fully glycosylated, cleaved HIV-1 envelope trimer journal March 2016
Accurate design of megadalton-scale two-component icosahedral protein complexes journal July 2016
Cell- and Protein-Directed Glycosylation of Native Cleaved HIV-1 Envelope journal June 2015
Influences on Trimerization and Aggregation of Soluble, Cleaved HIV-1 SOSIP Envelope Glycoprotein journal July 2013
HIV-1 Escape from a Peptidic Anchor Inhibitor through Stabilization of the Envelope Glycoprotein Spike journal September 2016
Murine Antibody Responses to Cleaved Soluble HIV-1 Envelope Trimers Are Highly Restricted in Specificity journal August 2015
Tiered Categorization of a Diverse Panel of HIV-1 Env Pseudoviruses for Assessment of Neutralizing Antibodies journal November 2009
Antigenicity and Immunogenicity of Transmitted/Founder, Consensus, and Chronic Envelope Glycoproteins of Human Immunodeficiency Virus Type 1 journal January 2013
Diverse Recombinant HIV-1 Envs Fail To Activate B Cells Expressing the Germline B Cell Receptors of the Broadly Neutralizing Anti-HIV-1 Antibodies PG9 and 447-52D journal December 2013
A Native-Like SOSIP.664 Trimer Based on an HIV-1 Subtype B env Gene journal January 2015
A Recombinant Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Complex Stabilized by an Intermolecular Disulfide Bond between the gp120 and gp41 Subunits Is an Antigenic Mimic of the Trimeric Virion-Associated Structure journal January 2000
Stabilization of the Soluble, Cleaved, Trimeric Form of the Envelope Glycoprotein Complex of Human Immunodeficiency Virus Type 1 journal September 2002
Enhancing the Proteolytic Maturation of Human Immunodeficiency Virus Type 1 Envelope Glycoproteins journal March 2002
Alphaherpesvirinae and Gammaherpesvirinae glycoprotein L and CMV UL130 originate from chemokines journal January 2013
Detailed characterization of antibody responses against HIV-1 group M consensus gp120 in rabbits journal December 2014
Presenting native-like HIV-1 envelope trimers on ferritin nanoparticles improves their immunogenicity journal September 2015
Recombinant HIV Envelope Proteins Fail to Engage Germline Versions of Anti-CD4bs bNAbs journal January 2013
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
Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer journal March 2015
Sequential and Simultaneous Immunization of Rabbits with HIV-1 Envelope Glycoprotein SOSIP.664 Trimers from Clades A, B and C journal September 2016
Epitopes for neutralizing antibodies induced by HIV-1 envelope glycoprotein BG505 SOSIP trimers in rabbits and macaques journal February 2018
Anti-HIV B Cell Lines as Candidate Vaccine Biosensors journal October 2012
Measuring HIV Neutralization in a Luciferase Reporter Gene Assay book January 2009
Exploring the gas access routes in a [NiFeSe] hydrogenase using crystals pressurized with krypton and oxygen journal August 2020
Changes in growth properties on passage in tissue culture of viruses derived from infectious molecular clones of HIV-1LAI, HIV-1MAL, and HIV-1ELI journal December 1991
Immunization with a synthetic consensus hepatitis C virus E2 glycoprotein ectodomain elicits virus-neutralizing antibodies journal December 2018
Germline-like predecessors of broadly neutralizing antibodies lack measurable binding to HIV-1 envelope glycoproteins: Implications for evasion of immune responses and design of vaccine immunogens journal December 2009
Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-neutralizing Epitopes journal December 2015
Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization journal August 2017
Site-Specific Glycosylation of Virion-Derived HIV-1 Env Is Mimicked by a Soluble Trimeric Immunogen journal August 2018
Rational Design of DNA-Expressed Stabilized Native-Like HIV-1 Envelope Trimers journal September 2018
Completeness of HIV-1 Envelope Glycan Shield at Transmission Determines Neutralization Breadth journal October 2018
HIV Vaccine Design to Target Germline Precursors of Glycan-Dependent Broadly Neutralizing Antibodies journal September 2016
Glycine Substitution at Helix-to-Coil Transitions Facilitates the Structural Determination of a Stabilized Subtype C HIV Envelope Glycoprotein journal May 2017
Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies journal May 2013
Structure and immune recognition of trimeric pre-fusion HIV-1 Env journal October 2014
Immunosilencing a Highly Immunogenic Protein Trimerization Domain journal January 2015
Design and crystal structure of a native-like HIV-1 envelope trimer that engages multiple broadly neutralizing antibody precursors in vivo journal August 2017
Dynamic light-scattering analysis of full-length human RPA14/32 dimer: purification, crystallization and self-association journal February 2001
Coot model-building tools for molecular graphics journal November 2004
Solving structures of protein complexes by molecular replacement with Phaser journal December 2006
MolProbity : all-atom structure validation for macromolecular crystallography journal December 2009
REFMAC 5 for the refinement of macromolecular crystal structures journal March 2011
Automated refinement of macromolecular structures at low resolution using prior information journal September 2016
Crystal Structure of a Soluble Cleaved HIV-1 Envelope Trimer journal October 2013
The microanatomic segregation of selection by apoptosis in the germinal center journal September 2017
Effects of Adjuvants on HIV-1 Envelope Glycoprotein SOSIP Trimers In Vitro journal April 2018
Comparison of Immunogenicity in Rhesus Macaques of Transmitted-Founder, HIV-1 Group M Consensus, and Trivalent Mosaic Envelope Vaccines Formulated as a DNA Prime, NYVAC, and Envelope Protein Boost journal April 2015
Cell- and Protein-Directed Glycosylation of Native Cleaved HIV-1 Envelope journal June 2015
Influences on Trimerization and Aggregation of Soluble, Cleaved HIV-1 SOSIP Envelope Glycoprotein journal July 2013
HIV-1 Escape from a Peptidic Anchor Inhibitor through Stabilization of the Envelope Glycoprotein Spike journal September 2016
Murine Antibody Responses to Cleaved Soluble HIV-1 Envelope Trimers Are Highly Restricted in Specificity journal August 2015
Immunogenicity in Rabbits of HIV-1 SOSIP Trimers from Clades A, B, and C, Given Individually, Sequentially, or in Combination journal January 2018
Tiered Categorization of a Diverse Panel of HIV-1 Env Pseudoviruses for Assessment of Neutralizing Antibodies journal November 2009
Antigenicity and Immunogenicity of Transmitted/Founder, Consensus, and Chronic Envelope Glycoproteins of Human Immunodeficiency Virus Type 1 journal January 2013
Structure-Guided Redesign Increases the Propensity of HIV Env To Generate Highly Stable Soluble Trimers journal December 2015
Diverse Recombinant HIV-1 Envs Fail To Activate B Cells Expressing the Germline B Cell Receptors of the Broadly Neutralizing Anti-HIV-1 Antibodies PG9 and 447-52D journal December 2013
A Native-Like SOSIP.664 Trimer Based on an HIV-1 Subtype B env Gene journal January 2015
A Recombinant Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Complex Stabilized by an Intermolecular Disulfide Bond between the gp120 and gp41 Subunits Is an Antigenic Mimic of the Trimeric Virion-Associated Structure journal January 2000
Stabilization of the Soluble, Cleaved, Trimeric Form of the Envelope Glycoprotein Complex of Human Immunodeficiency Virus Type 1 journal September 2002
Enhancing the Proteolytic Maturation of Human Immunodeficiency Virus Type 1 Envelope Glycoproteins journal March 2002
Rhesus macaques vaccinated with consensus envelopes elicit partially protective immune responses against SHIV SF162p4 challenge journal January 2013
Stabilizing HIV-1 envelope glycoprotein trimers to induce neutralizing antibodies journal September 2018
HIV-1 envelope glycoprotein immunogens to induce broadly neutralizing antibodies journal December 2015
Structure and immune recognition of trimeric pre-fusion HIV-1 Env text January 2014
Antigenicity and Immunogenicity of Transmitted/Founder, Consensus, and Chronic Envelope Glycoproteins of Human Immunodeficiency Virus Type 1 text January 2013
Recombinant HIV Envelope Proteins Fail to Engage Germline Versions of Anti-CD4bs bNAbs text January 2013

Cited By (9)

Nanoparticle Vaccines for Inducing HIV-1 Neutralizing Antibodies journal July 2019
V2-Specific Antibodies in HIV-1 Vaccine Research and Natural Infection: Controllers or Surrogate Markers journal August 2019
Viral Vectors for the Induction of Broadly Neutralizing Antibodies against HIV journal September 2019
HIV-1 Envelope and MPER Antibody Structures in Lipid Assemblies journal April 2020
Enhancing and shaping the immunogenicity of native-like HIV-1 envelope trimers with a two-component protein nanoparticle journal September 2019
Disruption of the HIV-1 Envelope allosteric network blocks CD4-induced rearrangements journal January 2020
Strategies for inducing effective neutralizing antibody responses against HIV-1 journal November 2019
Stabilized diverse HIV-1 envelope trimers for vaccine design journal January 2020
Stabilized diverse HIV-1 envelope trimers for vaccine design text January 2020

Similar Records

Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization
Journal Article · Mon Aug 21 20:00:00 EDT 2017 · Cell Reports · OSTI ID:1499807

Mapping the immunogenic landscape of near-native HIV-1 envelope trimers in non-human primates
Journal Article · Sun Aug 30 20:00:00 EDT 2020 · PLoS Pathogens · OSTI ID:1903966