Broad neutralization of human immunodeficiency virus type 1 mediated by plasma antibodies against the gp41 membrane proximal external region.
Elin S. Gray,Maphuti C. Madiga,Penny L. Moore,Koleka Mlisana,Salim S. Abdool Karim,James M. Binley,George M. Shaw,John R. Mascola,Lynn Morris +8 more
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TLDR
Data demonstrate the existence of MPER-specific cross-neutralizing antibodies in plasma, although the ability to elicit such potent antiviral antibodies during natural infection appears to be rare, Nevertheless, the identification of three novel antibody specificities within the MPER supports its further study as a promising target for vaccine design.Abstract:
We identified three cross-neutralizing plasma samples with high-titer anti-membrane proximal external region (MPER) peptide binding antibodies from among 156 chronically human immunodeficiency virus type 1-infected individuals. In order to establish if these antibodies were directly responsible for the observed neutralization breadth, we used MPER-coated magnetic beads to deplete plasmas of these specific antibodies. Depletion of anti-MPER antibodies from BB34, CAP206, and SAC21 resulted in 77%, 68%, and 46% decreases, respectively, in the number of viruses neutralized. Antibodies eluted from the beads showed neutralization profiles similar to those of the original plasmas, with potencies comparable to those of the known anti-MPER monoclonal antibodies (MAbs), 4E10, 2F5, and Z13e1. The anti-MPER neutralizing antibodies in BB34 were present in the immunoglobulin G3 subclass-enriched fraction. Alanine scanning of the MPER showed that the antibodies from these three plasmas had specificities distinct from those of the known MAbs, requiring one to three crucial residues at positions 670, 673, and 674. These data demonstrate the existence of MPER-specific cross-neutralizing antibodies in plasma, although the ability to elicit such potent antiviral antibodies during natural infection appears to be rare. Nevertheless, the identification of three novel antibody specificities within the MPER supports its further study as a promising target for vaccine design.read more
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Journal ArticleDOI
The immune response during acute HIV-1 infection: clues for vaccine development.
TL;DR: The finding that the first effective immune responses drive the selection of virus escape mutations provides insight into the earliest immune responses against the transmitted virus and their contributions to the control of acute viraemia.
Journal ArticleDOI
Broad and potent neutralization of HIV-1 by a gp41-specific human antibody
Jinghe Huang,Gilad Ofek,Leo B. Laub,Mark K. Louder,Nicole A. Doria-Rose,Nancy S. Longo,Hiromi Imamichi,Robert T. Bailer,Bimal K. Chakrabarti,Shailendra Kumar Sharma,S. Munir Alam,Tao Wang,Yongping Yang,Baoshan Zhang,Stephen A. Migueles,Richard T. Wyatt,Barton F. Haynes,Peter D. Kwong,John R. Mascola,Mark Connors +19 more
TL;DR: The structure of 10E8 in complex with the complete MPER revealed a site of vulnerability comprising a narrow stretch of highly conserved gp41-hydrophobic residues and a critical arginine or lysine just before the transmembrane region, suggesting the importance of these residues for neutralization.
Journal ArticleDOI
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
Elin S. Gray,Maphuti C. Madiga,Tandile Hermanus,Penny L. Moore,Constantinos Kurt Wibmer,Nancy Tumba,Lise. Werner,Koleka Mlisana,Sengeziwe Sibeko,Carolyn Williamson,Salim S. Abdool Karim,Lynn Morris +11 more
TL;DR: The data indicate that fewer than 20% of HIV-1 subtype C-infected individuals develop antibodies with cross-neutralizing activity after 3 years of infection and that these antibodies target different regions of the HIV- 1 envelope, including as yet uncharacterized epitopes.
Journal ArticleDOI
Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies
Peter D. Kwong,John R. Mascola +1 more
TL;DR: This work proposes an ontogeny and structure-based system of antibody classification that informs an understanding of the naive B cell repertoire, of somatic mutation, and of the resulting antibody features that are critical to effective HIV-1 neutralization.
Journal ArticleDOI
A limited number of antibody specificities mediate broad and potent serum neutralization in selected HIV-1 infected individuals.
Laura M. Walker,Melissa Simek,Frances Priddy,Johannes S. Gach,Denise Wagner,Michael B. Zwick,Sanjay Phogat,Pascal Poignard,Dennis R. Burton,Dennis R. Burton +9 more
TL;DR: The results suggest that broad and potent serum neutralization arises in most donors through a limited number of specificities (1–2 per donor), and that key N-linked glycans were critical for expression of the epitopes recognized by the bNAb specificities in the sera.
References
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Current protocols in immunology
TL;DR: Current Protocols in Immunology is a three-volume looseleaf manual that provides comprehensive coverage of immunological methods from classic to the most cutting edge, including antibody detection and preparation, assays for functional activities of mouse and human cells involved in immune responses, and animal models of autoimmune and inflammatory diseases.
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Rapid evolution of the neutralizing antibody response to HIV type 1 infection
TL;DR: Plasma virus continually and rapidly evolved to escape neutralization, indicating that neutralizing antibody exerts a level of selective pressure that has been underappreciated based on earlier, less comprehensive characterizations.
Journal ArticleDOI
Broadly neutralizing antibodies targeted to the membrane-proximal external region of human immunodeficiency virus type 1 glycoprotein gp41.
Michael B. Zwick,Aran F. Labrijn,Min Wang,Catherine Spenlehauer,Erica Ollmann Saphire,James M. Binley,John P. Moore,Gabriela Stiegler,Hermann Katinger,Dennis R. Burton,Paul W. H. I. Parren +10 more
TL;DR: The results suggest that a rather extensive region of gp41 close to the transmembrane domain is accessible to neutralizing Abs and could form a useful target for vaccine design.
Journal ArticleDOI
Comprehensive Cross-Clade Neutralization Analysis of a Panel of Anti-Human Immunodeficiency Virus Type 1 Monoclonal Antibodies
James M. Binley,Terri Wrin,Bette T. Korber,Michael B. Zwick,Min Wang,Colombe Chappey,Gabriela Stiegler,Renate Kunert,Susan Zolla-Pazner,Hermann Katinger,Christos J. Petropoulos,Dennis R. Burton +11 more
TL;DR: Broadly neutralizing monoclonal antibodies are potentially important tools in human immunodeficiency virus type 1 (HIV-1) vaccine design and have implications for passive-immunization studies in countries where clade C viruses are common, given that only MAbs b12 and 4E10 were effective against viruses from this clade.
Journal ArticleDOI
Cardiolipin Polyspecific Autoreactivity in Two Broadly Neutralizing HIV-1 Antibodies
Barton F. Haynes,Judith A. Fleming,E. William St. Clair,Herman Katinger,Gabriela Stiegler,Renate Kunert,James E. Robinson,Richard M. Scearce,Kelly Plonk,Herman F. Staats,Thomas L. Ortel,Hua-Xin Liao,S. Munir Alam +12 more
TL;DR: It is demonstrated that the two most broadly reactive HIV-1 envelope gp41 human mAbs, 2F5 and 4E10, are polyspecific autoantibodies reactive with the phospholipid cardiolipin, which may have important implications for generating effective neutralizing antibody responses by using HIV- 1 vaccines.
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