Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01

@article{Zhou2010StructuralBF,
  title={Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01},
  author={Tongqing Zhou and Ivelin S. Georgiev and Xueling Wu and Zhi-Yong Yang and Kaifan Dai and Andr{\'e}s Finzi and Young Do Kwon and Johannes F Scheid and Wei Shi and Ling Xu and Yongping Yang and Jiang Zhu and Michel C. Nussenzweig and Joseph G. Sodroski and Lawrence Shapiro and Gary J. Nabel and John R. Mascola and Peter D. Kwong},
  journal={Science},
  year={2010},
  volume={329},
  pages={811 - 817}
}
Designer Anti-HIV Developing a protective HIV vaccine remains a top global health priority. One strategy to identify potential vaccine candidates is to isolate broadly neutralizing antibodies from infected individuals and then attempt to elicit the same antibody response through vaccination (see the Perspective by Burton and Weiss). Wu et al. (p. 856, published online 8 July) now report the identification of three broadly neutralizing antibodies, isolated from an HIV-1–infected individual, that… 
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References

SHOWING 1-10 OF 46 REFERENCES
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.
Structural Basis of Immune Evasion at the Site of CD4 Attachment on HIV-1 gp120
TLDR
Co-crystal structures for two poorly neutralizing, CD4–binding site (CD4BS) antibodies, F105 and b13, in complexes with gp120 are determined, finding these conformations to be poorly compatible with the viral spike.
Structural definition of a conserved neutralization epitope on HIV-1 gp120
TLDR
A site of vulnerability, related to a functional requirement for efficient association with CD4, can therefore be targeted by antibody to neutralize HIV-1.
Maturation Pathways of Cross-Reactive HIV-1 Neutralizing Antibodies
TLDR
Evidence is presented that a germline-like b12 (monovalent and bivalent scFv as an Fc fusion protein or IgG) lacks measurable binding to an Env as measured by ELISA with a sensitivity in the μM range and that identifying antibodies that are intermediates in the pathways to maturation could help design novel vaccine immunogens to guide the immune system for their enhanced elicitation.
Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals
TLDR
This study reveals that by using appropriate screening methods, a large proportion of memory B cells can be isolated that produce mAbs with HIV-1 neutralizing activity, and three of these mAbs show unusual breadth of neutralization and therefore add to the current panel of HIV- 1 neutralizing antibodies with potential for passive protection and template-based vaccine design.
The antigenic structure of the HIV gp120 envelope glycoprotein
TLDR
The spatial organization of conserved neutralization epitopes on gp120 is described, using epitope maps in conjunction with the X-ray crystal structure of a ternary complex that includes a gp120 core, CD4 and a neutralizing antibody.
Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals
TLDR
The IgG memory B-cell compartment in the selected group of patients with broad serumneutralizing activity to HIV is comprised of multiple clonal responses with neutralizing activity directed against several epitopes on gp120.
Analysis of Neutralization Specificities in Polyclonal Sera Derived from Human Immunodeficiency Virus Type 1-Infected Individuals
TLDR
A systematic analysis of the NAb specificities of a panel of HIV-1-positive sera is presented, using methodologies that identify both conformational and continuous neutralization determinants on the HIV-2 Env protein and finds evidence that regions of the gp120 coreceptor binding site may also be a target of neutralizing activity.
Dissecting the Neutralizing Antibody Specificities of Broadly Neutralizing Sera from Human Immunodeficiency Virus Type 1-Infected Donors
TLDR
Overall, the data suggest that broad neutralization results from more than one specificity in the sera but that the number of these specificities is likely small.
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