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This article is part of the supplement: AIDS Vaccine 2012

Open Access Poster presentation

Comparison of the depth of vaccine-elicited HIV-1 Env epitope-specific CD8+ T lymphocyte responses

SL Hulot1*, BT Korber2, G Pantaleo3, J Tartaglia4, B Jacobs5, B Perdiguero6, CE Gomez6, M Esteban6, N Letvin1, MS Seaman1, B Haynes7 and S Santra1

  • * Corresponding author: SL Hulot

Author Affiliations

1 Beth Israel Deaconess Medical Center, Boston, MA, USA

2 Los Alamos National Laboratory, Los Alamos, NM, USA

3 Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland

4 Sanofi Pasteur, Toronto, Canada

5 Center for Infectious Diseases and Vaccinology, Tempe, AZ, USA

6 Centro Nacional de Biotecnologia, Madrid, Spain

7 Duke University Medical Center / Duke Human Vaccine Institute, Durham, NC, USA

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Retrovirology 2012, 9(Suppl 2):P288  doi:10.1186/1742-4690-9-S2-P288


The electronic version of this article is the complete one and can be found online at: http://www.retrovirology.com/content/9/S2/P288


Published:13 September 2012

© 2012 Hulot et al; licensee 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.

Background

One of the major challenges in the development of an effective HIV-1 vaccine is the extraordinary genetic diversity of the virus. Immunizations of nonhuman primates using consensus and mosaic immunogens have been shown to elicit cross-reactive CD8+T lymphocyte responses that increase the depth of epitope recognition. However, one of the limitations of vaccine-induced epitope-specific CD8+T lymphocytes includes lack of protection against diverse strains and emergent forms of HIV-1 due to altered T cell receptor (TCR) affinity for variant peptide:MHC class I complexes.

Methods

In this study, we immunized a cohort of fifteen Mamu-A*01+ rhesus monkeys with either a 3-valent mosaic Env, group M consensus Env, or single clade B Env vaccine and compared the ability of the CD8+T lymphocyte populations elicited by each immunogen to recognize variants of an HIV-1 envelope epitope sequence p41A (YI9). We identified vaccine-induced CD8+T lymphocytes populations using tetramers constructed with 9 variants of p41A epitope. We assessed the ability of those variant peptides to activate CTL by measuring cytokine production and CD107a expression. We evaluated proliferation using carboxyfluorescein succinimidyl ester. Finally, we investigated the functional avidity of these CD8+T lymphocytes for the variant peptide:Mamu-A*01 complexes using surface plasmon resonance technology.

Results

Our data show that Env immunizations can generate cross-reactive CD8+T lymphocytes that recognize 2 of 9 (22%) of the variants of p41A epitope, with higher responses induced by the consensus and the 3-valent mosaic immunogens (variant from clade C and variant from clade A/E) compared to the single clade Env immunogen. Tetramer-binding data also show that CD8+ T lymphocytes from monkeys immunized with mosaic immunogen have a trend of higher binding to majority of the variant peptides tested.

Conclusion

This underscores the potential of mosaic immunogens for generating cellular immune responses with greater depth.