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Volume 9 Supplement 2

AIDS Vaccine 2012

Structural definition for a new modality of broad and potent antibody neutralization at the CD4-binding site on HIV-1 gp120


The initial site of CD4-attachment on HIV-1 gp120 is vulnerable to neutralizing antibodies, and a number of such antibodies have been found that target this site. One set of antibodies, represented by VRC01, mimic CD4 in their recognition and utilize a common V-gene origin (VH1-2*02). Another set of antibodies, represented by the recently identified VRC13, derives from VH1-69*01 and is able to neutralize over 90% of circulating HIV-1 isolates, including isolates resistant to VRC01. Do the VRC13-like antibodies also mimic CD4, or do they represent a new modality of effective CD4-binding-site neutralization?


To define the mode of recognition used by VRC13, we crystallized its antigen-binding fragment in complex with HIV-1 gp120, from both VRC01-sensitive and VRC01-resistant strains, and determined these X-ray structures.


The structure of VRC13 indicates a mode of recognition rotated by 45 degrees and translated ~10 Å from that of VRC01, although both VRC01 and VRC13 utilize similar angles of approach. Unlike VRC01-like antibodies, which feature gp120 contacts primarily in the heavy chain 2nd complementarity determining region (CDR H2), VRC13 utilizes a long heavy chain CDR H3 to contact the CD4-binding site. Overall, the structural details of VRC13 do not mimic those of CD4.


Broad and potent neutralization at the CD4-binding site is not limited to the VRC01-mode of CD4 mimicry. A new mode of effective HIV-1 neutralization, which is defined by the VRC13-gp120 structure and utilizes CDR H3 recognition, may serve as an additional template for the design of an effective HIV-1 vaccine. The natural diversity of the CDR H3 – a product of V-D-J recombination – may provide advantages in the elicitation of VRC13-like antibodies.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Zhou, T., Moquin, S., Lynch, R. et al. Structural definition for a new modality of broad and potent antibody neutralization at the CD4-binding site on HIV-1 gp120. Retrovirology 9 (Suppl 2), P57 (2012).

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  • Heavy Chain
  • Complementarity Determine Region
  • Structural Definition
  • Potent Neutralization
  • Similar Angle