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Volume 9 Supplement 2

AIDS Vaccine 2012

  • Poster presentation
  • Open Access

Mutations in the V1 domain of Thai CRF01-AE viruses that confer sensitivity/resistance to broadly neutralizing antibodies

  • 2,
  • 2,
  • 2,
  • 1,
  • 2,
  • 2,
  • 1 and
  • 1
Retrovirology20129 (Suppl 2) :P106

https://doi.org/10.1186/1742-4690-9-S2-P106

  • Published:

Keywords

  • Clinical Trial
  • Infectious Disease
  • Cancer Research
  • Structural Study
  • Infected Individual

Background

Antibodies to the V1/V2 domain of gp120 have recently been identified as a correlate of protection in the RV144 clinical trial. To better understand the specificity of broadly neutralizing antibodies) to the V1/V2 domain of Thai CRF01_AE viruses, we analyzed the specificity of antibodies in HIV+ elite neutralizer (EN) sera by swarm analysis.

Methods

Swarm analysis makes use of the swarm of closely envelope variants that evolve in each HIV-1 infected individual, as a source of naturally occurring and biologically relevant mutations that confer neutralization sensitivity/resistance. Envelopes from clade B and CRF01_AE viruses were tested for neutralization sensitivity/resistance with sera from ENs infected with clade B and CRF01_AE viruses.

Results

We found five mutations in the V1 domain that affected neutralization sensitivity/ resistance of CRF01_AE viruses. This differed from clade B viruses in which mutations altering neutralization sensitivity/resistance clustered in the V2 domain. Structural studies have shown that the V1/V2 domain of gp120 consists of a four-stranded β-sheet structure. We found that mutations affecting neutralization sensitivity/resistance in Thai CRF01_AE viruses clustered around the exposed turn at the junction of the A-B strands. In contrast, the mutations that altered neutralization sensitivity/resistance in clade B viruses clustered around exposed turns at the junction of the B-C and the C-D strands.

Conclusion

The present studies suggest that there is a major difference in the antigenic structure of the V1V2 domain between clade B and CRF01_AE envelope proteins. These results suggest that antibodies to the V1 domain of CRF01_AE envelope proteins should be evaluated as a correlate of protection in the RV144 trial. For this purpose, studies using novel proteins and scaffolds, that replicate the structure of conformation- and glycoform- dependent epitopes in the V1/V2 domain, are under investigation.

Authors’ Affiliations

(1)
Monogram Biosciences, San Francisco, CA, USA
(2)
Monogram Biosciences, San Francisco, CA, USA

Copyright

© O'Rourke 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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