Volume 9 Supplement 2

AIDS Vaccine 2012

Open Access

Characteristics of HIV-1 gp120 molecules that bind ancestor, intermediate and mature forms of VRC01-like antibodies

  • M Joyce1,
  • B Zhang1,
  • T Zhou1,
  • S Moquin1,
  • X Wu1,
  • M Louder1,
  • Z Zhang1,
  • I Georgiev1,
  • J Zhu1,
  • L Shapiro1,
  • JR Mascola1,
  • GJ Nabel1 and
  • PD Kwong1
Retrovirology20129(Suppl 2):P68

DOI: 10.1186/1742-4690-9-S2-P68

Published: 13 September 2012

Background

A group of highly effective neutralizing antibodies, which target the site of CD4 binding on HIV-1 gp120, have recently been identified. These antibodies – called VRC01-like antibodies – all originate from the same VH1-2*02 germline gene and, while the mature antibodies have undergone extensive maturation via non-homologous pathways, their recognition of the CD4-binding site of gp120 is similar. An efficacious vaccine that elicits VRC01-like antibodies will likely be required to bind to VH1-2*02-derived B cells to initiate their expansion and subsequent maturation, however, binding studies with reverted-ancestor VRC01-like antibodies and HIV-1 gp120 molecules typically show binding that is too weak to initiate B cell maturation.

Methods

To identify HIV-1 gp120 molecules capable of interacting with reverted-ancestor molecules with sufficient affinity to initiate B cell maturation, we screened large panels of HIV-1 pseudoviruses for sensitivity to reverted-ancestor forms of VRC01-like antibodies. Identified HIV-1 strains (and related gp120s) were then analyzed for recognition to a panel of diverse VRC01-like antibodies.

Results

No HIV-1 strains were identified which could be neutralized by reverted heavy chain- and light chain-ancestors of VRC01-like antibodies. Chimeric forms of the VRC01-like antibodies with reverted and mature heavy/light chain mixtures did, however, neutralize a small subset of HIV-1 isolates. Characterization of gp120s from the sensitive subset found measurable affinity to the ancestral forms of VRC01-like antibodies. In comparison, typical gp120 molecules, e.g. YU2 gp120, fail to bind low-divergent forms of the VRC01-like antibodies, i.e. those with less than 10% divergence from germline.

Conclusion

Select strains of HIV-1 can interact with ancestral forms of VRC01-like antibodies. Defining the specific characteristics of these select strains should enable identification of gp120-derived immunogens capable of productive interactions with VH1-2*02-derived B cells.

Authors’ Affiliations

(1)
Vaccine Research Center, NIAID/NIH

Copyright

© Joyce et al; licensee BioMed Central Ltd. 2012

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 (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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