Broad and potent neutralization of HIV-1 by a gp41-specific human antibody

@article{Huang2012BroadAP,
  title={Broad and potent neutralization of HIV-1 by a gp41-specific human antibody},
  author={Jinghe Huang and Gilad Ofek and Leo Laub and Mark K. Louder and Nicole A. Doria-Rose and Nancy S. Longo and Hiromi Imamichi and Robert T. Bailer and Bimal K. Chakrabarti and Shailendra Kumar Sharma and S. Munir Alam and Tao Wang and Yongping Yang and Baoshan Zhang and Stephen A. Migueles and Richard T. Wyatt and Barton F. Haynes and Peter D. Kwong and John R. Mascola and Mark Connors},
  journal={Nature},
  year={2012},
  volume={491},
  pages={406 - 412}
}
Characterization of human monoclonal antibodies is providing considerable insight into mechanisms of broad HIV-1 neutralization. Here we report an HIV-1 gp41 membrane-proximal external region (MPER)-specific antibody, named 10E8, which neutralizes ∼98% of tested viruses. An analysis of sera from 78 healthy HIV-1-infected donors demonstrated that 27% contained MPER-specific antibodies and 8% contained 10E8-like specificities. In contrast to other neutralizing MPER antibodies, 10E8 did not bind… 
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References

SHOWING 1-10 OF 69 REFERENCES
Role of HIV membrane in neutralization by two broadly neutralizing antibodies
TLDR
It is proposed that these antibodies associate with the viral membrane in a required first step and are thereby poised to capture the transient gp41 fusion intermediate, which bears directly on strategies for rational design of HIV-1 envelope immunogens.
Broadly Neutralizing Antibodies Targeted to the Membrane-Proximal External Region of Human Immunodeficiency Virus Type 1 Glycoprotein gp41
TLDR
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.
A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1
TLDR
Since sequence variability of neutralizing epitopes is considered to be a major obstacle to HIV-1 vaccine development, the conserved B-cell epitope described here is a promising candidate for inclusion in a vaccine against AIDS.
Isolation of a Human Anti-HIV gp41 Membrane Proximal Region Neutralizing Antibody by Antigen-Specific Single B Cell Sorting
TLDR
The isolated recombinant mAb, CAP206-CH12, utilized a portion of the distal MPER and neutralized a subset of HIV-1 pseudoviruses sensitive to CAP206 plasma antibodies, suggesting that gp41 neutralizing epitopes may interact with a restricted set of naive B cells during HIV- 1 infection.
Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1
TLDR
Three broadly neutralizing antibodies are identified, isolated from an HIV-1–infected individual, that exhibited great breadth and potency of neutralization and were specific for the co-receptor CD4-binding site of the glycoprotein 120 (gp120), part of the viral Env spike.
Polyclonal B Cell Responses to Conserved Neutralization Epitopes in a Subset of HIV-1-Infected Individuals
TLDR
The broadly reactive HIV-1 neutralization observed in some subjects is mediated by antibodies targeting several conserved regions on the HIV- 1 envelope glycoprotein.
Potent and Broad Neutralization of HIV-1 Subtype C by Plasma Antibodies Targeting a Quaternary Epitope Including Residues in the V2 Loop
TLDR
Comparison of the CAP256 epitope with that of the PG9/PG16 monoclonal antibodies suggested that these epitopes overlapped, adding to the mounting evidence that this may represent a common neutralization target that should be further investigated as a potential vaccine candidate.
A fusion-intermediate state of HIV-1 gp41 targeted by broadly neutralizing antibodies
TLDR
It is found that their epitopes, in the membrane-proximal segment of the envelope protein ectodomain, are exposed only on a form designed to mimic an intermediate state during viral entry, which helps explain the rarity of 2F5- and 4E10-like antibody responses and suggest a strategy for eliciting them.
Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing
TLDR
Broadly neutralizing HIV-1 immunity associated with VRC01-like antibodies thus involves the evolution of antibodies to a highly affinity-matured state required to recognize an invariant viral structure, with lineages defined from thousands of sequences providing a genetic roadmap of their development.
Selection Pressure on HIV-1 Envelope by Broadly Neutralizing Antibodies to the Conserved CD4-Binding Site
TLDR
Data indicate that the CD4bs-directed neutralizing antibodies exert ongoing selection pressure on the conservedCD4bs epitope of HIV-1 Env.
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