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Volume 9 Supplement 2

AIDS Vaccine 2012

  • Poster presentation
  • Open Access

Mapping of SIVmac T-cell epitopes in cynomolgus macaques immunized with auxo-GTU-MultiSIV DNA by the intradermal route followed by electroporation

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Retrovirology20129 (Suppl 2) :P34

https://doi.org/10.1186/1742-4690-9-S2-P34

  • Published:

Keywords

  • Peptide
  • Cell Response
  • Vaccine Development
  • Microsatellite Analysis
  • Specific Immune Response

Background

Intradermal immunization with electroporation using auxo-GTU-MultiHIV DNA encoding Gag, Nef, Rev and Tat induces strong and sustained T cell responses in cynomolgus macaques. Here, we used an equivalent vaccine encoding SIVmac239 antigens (Gag, Nef, Rev, Tat, Vif, Vpx and Vpr) and we described the breath of this T cell response.

Methods

Naïve male mauritian cynomolgus macaques were immunized with auxo-GTU-MultiSIV DNA encoding Gag, Nef, Rev and Tat (n=14) or by a combination of auxo-GTU-MultiSIV DNA and auxo-GTU-SIV-vifvprvpx (n=12) by the intradermal route followed by electroporation. MHC class I and class II haplotypes were determined by microsatellite analysis. T-cell epitopes were mapped by IFN-γ ELISPOT in PBMC by using matrix of 15-mer (overlapping by 11) SIVmac239 Gag, Nef, Rev, Tat, Vif, Vpx and Vpr peptides. Sequence and length of candidate epitopes were further optimized.

Results

Immunization induced intense and sustained IFN-γ ELISPOT responses in peripheral blood. T-cell responses against MHC class I epitopes were evidenced: two in Gag p15 (KA10(28-37) presented by Mafa-B*011:01 and EL10(58-68) presented by a MHC-Ia molecule from haplotype M3), two in Gag p27 (HL9(146-154) presented by Mafa-B*075:01 and LA9(189-197) presented by a MHC-Ib from haplotype M1), three in Nef (AS10(4-13) presented by a MHC-Ib molecule from haplotype M3; RM9(103-111) presented by Mafa-A1*063:02; LD10(146-155) presented by a MHC-Ia from haplotype M1M2M3), one in Rev (SP10(59-68) presented by Mafa-B*075:01), one in Tat (CF9(59-67) presented by Mafa-A1*063:02), four in Vif and two in Vpx. One MHC class II epitope was identified in Gag p27 (haplotype M3). Among these, to our knowledge, AF11 is a newly described epitope in cynomolgus macaques.

Conclusion

Auxo-GTU-MultiSIV DNA vaccination followed by electroporation induced multi-epitopic T cell responses, essentially CD8+ but also CD4+. Determination of SIV T-cell epitopes in cynomolgus macaques facilitates the monitoring of specific immune responses and pre-clinical vaccine development in this model.

Authors’ Affiliations

(1)
Laboratoire D'Immunogénétique Moléculaire EA 3034, Faculté de Médecine, Toulouse, France
(2)
FIT Biotech, Tampere, Finland
(3)
CEA, Fontenay-aux-Roses, France

Copyright

© Corneau 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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