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Abstract
Strategies to overcome immunodominance & the potential role of subdominant CTL epitopes against virus challenge
Im E.-J.1, McMichael A.J.1, Hanke T.1
Introduction: The aim for an effective CTL epitope-based HIV vaccine is the induction of broad CTL responses which will decrease the likelihood of viral escape from immune recognition. The phenomenon of immunodominance, however, results in a T cell response that is largely focused on only a few dominant epitopes, rendering the majority of other (i.e. subdominant) epitopes ineffective. A candidate HIV clade A vaccine, HIVA is based on the p17/p24 gag region and a string of CTL epitopes. Thus far, the immunodominance hierarchy has been determined to be, H(gp120)>P(pol)>G1(p24)>G2(p24). Serial removal of dominant epitopes by deletion or mutation in the order of immunodminance hierarchy has been performed and cloned into DNA and vaccinia virus (WR strain). To emphasize the importance of the subdominant epitopes against viral challenge, groups of mice were given two doses of DNA and then challenged with WR.
Methods: Ag-specific CD8 T cell responses were detected using IFN-ELISPOT, ICS and in vivo lysis assay using fluorescent labels CFSE/CMTMR. Peptide-MHC class I binding affinity was measured using T2 cell lines expressing Kd/Dd. Viral titer was calculated with the separted ovaries.
Conclusions: After serial removal of dominant epitopes, subdominant epitope-specific CD8 T cell responses were serially recovered and viral titer lowered. This study provides important information of what could happen during viral escape. Therefore, it is better to rely on more epitopes than a single dominant epitope.
The 3rd IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
TuPe13.3B01
Suggested Citation
"ImE.-J., et al.
Strategies to overcome immunodominance & the potential role of subdominant CTL epitopes against virus challenge.
Poster Exhibition:
The 3rd IAS Conference on HIV Pathogenesis and Treatment:
Abstract no.
TuPe13.3B01"
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