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Volume 9 Supplement 2

AIDS Vaccine 2012

  • Poster presentation
  • Open Access

Breadth or conservation score (CS): which is more important for HIV-1 T cell based vaccine immunogen design?

  • 1,
  • 2,
  • 2,
  • 3,
  • 4,
  • 2,
  • 2 and
  • 5
Retrovirology20129 (Suppl 2) :P260

https://doi.org/10.1186/1742-4690-9-S2-P260

  • Published:

Keywords

  • Viral Load
  • Early Infection
  • Conservation Score
  • Lower Viral Load
  • Antiviral Efficacy

Background

One of the greatest challenges to develop an efficacious HIV vaccine is the enormous diversity of HIV-1. To tackle this problem, T cells based vaccine approaches have come up with two main camps: the mosaic immunogen camp: increasing the breadth of vaccine-induced responses, and the conserved immunogen camp: targeting vaccine-induced T-cell responses only to highly conserved viral regions. While both approaches are theoretically sound, there is no current data suggesting that either approach will be successful in inducing T cells with superior antiviral efficacy. Here we analyzed T cell responses elicited during early HIV-1 infection, to address the question whether CS of targeted epitopes and breadth of T cell responses play an important role in viral control.

Methods

Using IFN-γ ELISpot, we comprehensively mapped T cell epitope specificities recognized by 24 ART-naïve individuals during early infection. We identified CS of targeted epitopes, where the CS is defined as the proportion of random HIV-1 group M amino acid sequences in the LANL database that include the epitope. We used a prediction model to impute the viral load (VL) set-point using the first available VL as a predictor for subjects lacking VL set-point. We further evaluated the association between the CS of the targeted epitopes and breadth of T cell responses to the individuals’ VL set-point.

Results

The breadth of CD8+ T cell responses inversely correlated with VL set-point (r=-0.46, p=0.025). Subjects possessing CD8+ T cells recognizing at least one conserved epitope had a lower VL set-point compared to those recognizing only variable epitopes (p=0.093).

Conclusion

Breadth and CS of HIV-specific CD8+ T cells elicited during early infection are both important for controlling viral replication in vivo. Rationale design of immunization approaches should aim at eliciting a greater breadth of CD8+ T cell to conserved epitopes.

This project is funded by NIH grant#R01AI090783.

Authors’ Affiliations

(1)
University of Washington/Seattle Biomedical Research Institute, Seattle, WA, USA
(2)
Statistical Center for HIV/AIDS Research & Prevention (SCHARP), Seattle, WA, USA
(3)
Department of Microbiology, University of Washington, Seattle, WA, USA
(4)
Department of Medicine, University of Washington, Seattle, WA, USA
(5)
Seattle Biomedical Research Institute, Seattle, WA, USA

Copyright

© Kunwar 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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