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Volume 9 Supplement 2

AIDS Vaccine 2012

  • Poster presentation
  • Open Access

Immunodominance and viral ditness in Gag may contribute to differential viral control in HLA-B*7 supertype individuals acutely infected with HIV-1C

  • 1,
  • 1,
  • 1,
  • 1,
  • 1,
  • 1,
  • 1,
  • 1,
  • 1,
  • 2 and
  • 3
Retrovirology20129 (Suppl 2) :P160

https://doi.org/10.1186/1742-4690-9-S2-P160

  • Published:

Keywords

  • Cell Response
  • ELIspot Assay
  • Viral Control
  • Cell Immune Response
  • Escape Mutation

Background

HLA-B*7 supertype alleles are common among people of African descent and are associated with viral control. In particular, HLA-B*81 has been previously associated with reduced viral fitness. We analyzed the immunodominance of CD8+ T cell responses targeted by the B*7 supertype alleles, viral evolution and fitness dynamics over 1yr in acutely infected patients.

Methods

Six HLA-B*7 supertype participants [HLA-B*81 (n=2), HLA-B*4201 (n=3) and HLA-B*4202 (n=1)] identified with acute HIV-1 infection (antibody negative, vRNA positive) in KwaZulu-Natal, South Africa were studied. CD8+ T cell responses were measured by the IFN-γ ELIspot assay. Replication capacities of viruses encoding Gag-protease were measured. Full-length HIV-1 Gag clonal sequencing of plasma was performed at ~14 days post infection and 1yr later.

Results

The average viral set point of the 4 HLA-B*42 individuals was higher than the 2 HLA-B*81, 4.89 vs 4.16 respectively. Approximately 28 days after viral infection, CD8+ T cell responses were directed to an average of 2/5 (range 2-4) HLA-B*42 Gag-specific epitopes, median magnitude of 490 (range 170–2,480 SFC/million PBMCs). None of these 4 individuals had selected for escape mutations in the immunodominant TL9 epitope at 1yr post-infection. Interestingly, CD8+ T cell responses were only against the TL9 epitope for the 2 HLA-B*81 patients with a median magnitude of 950 (range 300–1780 SFC/million PBMCs). One patient had a single wild type epitope in the transmitted virus, compared to 4/5 wild type epitopes in the second patient. However, CD8+ T cell responses were only elicited at the TL9 epitope with a low magnitude against T186S in the 1 patient with a much lower viral fitness.

Conclusion

Strong, rather than broad immunodominant responses in HLA-B*7 individuals is desirable in viral control. Furthermore, this study emphasizes the advantage of early dominant CD8+ T cell immune responses and an attenuated virus in conferring clinical benefit among HLA-B*7 supertype individuals.

Authors’ Affiliations

(1)
University of KwaZulu-Natal, Durban, South Africa
(2)
University of Oxford, Oxford, UK
(3)
Ragon Institute of Massachusetts General Hospital, MIT and Harvard, Boston, MA, USA

Copyright

© Gounder 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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