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

Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site

Journal Article · · Cell Reports
 [1];  [2];  [3];  [2];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [4];  [5];  [1];  [6] more »;  [1];  [1];  [1];  [1];  [7];  [2];  [8];  [1] « less
  1. Duke Univ. School of Medicine, Durham, NC (United States)
  2. Harvard Medical School, Boston, MA (United States)
  3. National Inst. for Communicable Diseases, Johannesburg (South Africa); Univ. of the Witwatersrand, Johannesburg (South Africa)
  4. Univ. of KwaZulu-Natal, Durban (South Africa); Columbia Univ., New York, NY (United States)
  5. Novartis Vaccines and Diagnostics, Inc., Cambridge, MA (United States)
  6. Boston Univ., MA (United States)
  7. National Inst. for Communicable Diseases, Johannesburg (South Africa); Univ. of KwaZulu-Natal, Durban (South Africa); Univ. of the Witwatersrand, Johannesburg (South Africa)
  8. Harvard Medical School, Boston, MA (United States); Howard Hughes Medical Inst., Boston, MA (United States)
+ Show Author Affiliations
Antibodies that neutralize autologous transmitted/founder (TF) HIV occur in most HIV-infected individuals and can evolve to neutralization breadth. Autologous neutralizing antibodies (nAbs) against neutralization-resistant (Tier-2) viruses are rarely induced by vaccination. Whereas broadly neutralizing antibody (bnAb)-HIV-Envelope structures have been defined, the structures of autologous nAbs have not. Here, we show that immunization with TF mutant Envs gp140 oligomers induced high-titer, V5-dependent plasma neutralization for a Tier-2 autologous TF evolved mutant virus. Structural analysis of autologous nAb DH427 revealed binding to V5, demonstrating the source of narrow nAb specificity and explaining the failure to acquire breadth. Thus, oligomeric TF Envs can elicit autologous nAbs to Tier-2 HIVs, but induction of bnAbs will require targeting of precursors of B cell lineages that can mature to heterologous neutralization.
Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
NIH/NIAID/DAIDS
OSTI ID:
1234757
Journal Information:
Cell Reports, Journal Name: Cell Reports Journal Issue: 1 Vol. 14; ISSN 2211-1247
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
ENGLISH

References (57)

Is clearance of HIV-1 viraemia at seroconversion mediated by neutralising antibodies? journal November 1992
Cooperation of B Cell Lineages in Induction of HIV-1-Broadly Neutralizing Antibodies journal July 2014
Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies journal September 2012
Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals journal March 2009
Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus journal April 2013
Rapid evolution of the neutralizing antibody response to HIV type 1 infection journal March 2003
Affinity maturation in an HIV broadly neutralizing B-cell lineage through reorientation of variable domains journal June 2014
Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated journal October 2011
Engineering HIV envelope protein to activate germline B cell receptors of broadly neutralizing anti-CD4 binding site antibodies journal March 2013
SoDA2: a Hidden Markov Model approach for identification of immunoglobulin rearrangements journal February 2010
Crystal Structure of a Soluble Cleaved HIV-1 Envelope Trimer journal October 2013
Host Controls of HIV Neutralizing Antibodies journal May 2014
Broad Neutralization of Human Immunodeficiency Virus Type 1 Mediated by Plasma Antibodies against the gp41 Membrane Proximal External Region journal August 2009
Taking Care of Unfinished Business and the Business of the 21st Century journal August 2012
MolProbity: all-atom contacts and structure validation for proteins and nucleic acids text January 2007
Is clearance of HIV-1 viraemia at seroconversion mediated by neutralising antibodies? journal November 1992
[20] Processing of X-ray diffraction data collected in oscillation mode book January 1997
Immunoglobulin Gene Insertions and Deletions in the Affinity Maturation of HIV-1 Broadly Reactive Neutralizing Antibodies journal September 2014
A FAM21-Containing WASH Complex Regulates Retromer-Dependent Sorting journal November 2009
Antibody Light-Chain-Restricted Recognition of the Site of Immune Pressure in the RV144 HIV-1 Vaccine Trial Is Phylogenetically Conserved journal December 2014
Optimization and validation of the TZM-bl assay for standardized assessments of neutralizing antibodies against HIV-1 journal July 2014
High-throughput isolation of immunoglobulin genes from single human B cells and expression as monoclonal antibodies journal June 2009
Antibody neutralization and escape by HIV-1 journal March 2003
Structural definition of a conserved neutralization epitope on HIV-1 gp120 journal February 2007
Molecular architecture of native HIV-1 gp120 trimers journal July 2008
Broad neutralization coverage of HIV by multiple highly potent antibodies journal September 2011
Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies journal March 2014
Broadly neutralizing antibodies and the search for an HIV-1 vaccine: the end of the beginning journal August 2013
Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection journal May 2008
Identification of autoantigens recognized by the 2F5 and 4E10 broadly neutralizing HIV-1 antibodies journal January 2013
MolProbity: all-atom contacts and structure validation for proteins and nucleic acids journal May 2007
Coot model-building tools for molecular graphics journal November 2004
Solving structures of protein complexes by molecular replacement with Phaser journal December 2006
XDS journal January 2010
PHENIX: a comprehensive Python-based system for macromolecular structure solution journal January 2010
Overview of the CCP 4 suite and current developments journal March 2011
HIV-1 neutralizing antibodies: understanding nature's pathways journal June 2013
Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01 journal July 2010
Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 Binding journal July 2011
Broadly Neutralizing Antibodies Present New Prospects to Counter Highly Antigenically Diverse Viruses journal July 2012
The HIV-1 Envelope Glycoproteins: Fusogens, Antigens, and Immunogens journal June 1998
HIV-1 neutralizing antibodies induced by native-like envelope trimers journal June 2015
The Neutralization Breadth of HIV-1 Develops Incrementally over Four Years and Is Associated with CD4+ T Cell Decline and High Viral Load during Acute Infection journal March 2011
Neutralizing Antibody Responses in Acute Human Immunodeficiency Virus Type 1 Subtype C Infection journal April 2007
Antibody Specificities Associated with Neutralization Breadth in Plasma from Human Immunodeficiency Virus Type 1 Subtype C-Infected Blood Donors journal June 2009
Broad Neutralization of Human Immunodeficiency Virus Type 1 Mediated by Plasma Antibodies against the gp41 Membrane Proximal External Region journal August 2009
Breadth of Human Immunodeficiency Virus-Specific Neutralizing Activity in Sera: Clustering Analysis and Association with Clinical Variables journal November 2009
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
A Native-Like SOSIP.664 Trimer Based on an HIV-1 Subtype B env Gene journal January 2015
Polyclonal B Cell Responses to Conserved Neutralization Epitopes in a Subset of HIV-1-Infected Individuals journal August 2011
Differential Reactivity of Germ Line Allelic Variants of a Broadly Neutralizing HIV-1 Antibody to a gp41 Fusion Intermediate Conformation journal September 2011
Control of Viremia and Prevention of Simian-Human Immunodeficiency Virus-Induced Disease in Rhesus Macaques Immunized with Recombinant Vaccinia Viruses plus Inactivated Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 1 Particles journal January 2003
Reconstructing a B-cell clonal lineage. I. Statistical inference of unobserved ancestors journal January 2013
Isolation of a Human Anti-HIV gp41 Membrane Proximal Region Neutralizing Antibody by Antigen-Specific Single B Cell Sorting journal September 2011
Early Low-Titer Neutralizing Antibodies Impede HIV-1 Replication and Select for Virus Escape journal May 2012
Viral Escape from HIV-1 Neutralizing Antibodies Drives Increased Plasma Neutralization Breadth through Sequential Recognition of Multiple Epitopes and Immunotypes journal October 2013

Cited By (17)

RAB11FIP5 Expression and Altered Natural Killer Cell Function Are Associated with Induction of HIV Broadly Neutralizing Antibody Responses journal October 2018
Holes in the Glycan Shield of the Native HIV Envelope Are a Target of Trimer-Elicited Neutralizing Antibodies journal August 2016
Completeness of HIV-1 Envelope Glycan Shield at Transmission Determines Neutralization Breadth journal October 2018
Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity journal October 2016
Brief introduction of current technologies in isolation of broadly neutralizing HIV-1 antibodies journal January 2018
Identification and specificity of broadly neutralizing antibodies against HIV journal January 2017
Immunologic characteristics of HIV-infected individuals who make broadly neutralizing antibodies journal January 2017
Neutralizing Antibody Responses following Long-Term Vaccination with HIV-1 Env gp140 in Guinea Pigs journal July 2018
HIV-1 immunogens and strategies to drive antibody responses towards neutralization breadth journal November 2018
Boosting of HIV envelope CD4 binding site antibodies with long variable heavy third complementarity determining region in the randomized double blind RV305 HIV-1 vaccine trial journal February 2017
Somatic hypermutation to counter a globally rare viral immunotype drove off-track antibodies in the CAP256-VRC26 HIV-1 V2-directed bNAb lineage journal September 2019
Advances in HIV-1 Vaccine Development journal April 2018
Native-like Env trimers as a platform for HIV-1 vaccine design journal January 2017
Induction of Heterologous Tier 2 HIV-1-Neutralizing and Cross-Reactive V1/V2-Specific Antibodies in Rabbits by Prime-Boost Immunization journal July 2016
Structure of an N276-Dependent HIV-1 Neutralizing Antibody Targeting a Rare V5 Glycan Hole Adjacent to the CD4 Binding Site journal August 2016
Immunogenicity of NYVAC Prime-Protein Boost Human Immunodeficiency Virus Type 1 Envelope Vaccination and Simian-Human Immunodeficiency Virus Challenge of Nonhuman Primates journal February 2018
Quantification of the Resilience and Vulnerability of HIV-1 Native Glycan Shield at Atomistic Detail journal January 2020

Similar Records

HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design
Journal Article · Mon Dec 31 23:00:00 EST 2018 · Cell Host & Microbe · OSTI ID:1623654
Viral Envelope Evolution in Simian–HIV-Infected Neonate and Adult-Dam Pairs of Rhesus Macaques
Journal Article · Tue Jun 25 00:00:00 EDT 2024 · Viruses · OSTI ID:2470525
Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization
Journal Article · Tue Aug 22 00:00:00 EDT 2017 · Cell Reports · OSTI ID:1499807

Related Subjects

59 BASIC BIOLOGICAL SCIENCES