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Volume 6 Supplement 3

AIDS Vaccine 2009

P19-44. Priming with a DNA vaccine enconding HIV CD4+ T cell epitopes enhances responses against subsequent immunization with plasmid encoding Vif

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Background

Since none of the developed candidate vaccines against HIV has been effective, novel vaccine concepts are needed. Our group has identified conserved HIV CD4+ T cell epitopes binding promiscuously to multiple HLA-DR molecules, and frequently recognized by HIV-1-infected patients. A DNA vaccine encoding such epitopes (pVAX-HIVBr18) showed strong cellular responses in mice. An early CD8+ T cell response against Vif is associated with control of SIV infection in primates. A vaccine capable of stimulating both CD4+ and CD8+ T cells can be useful to establish an appropriate immune control of HIV. We aim to test whether preimmunization with pVAX-HIVBr18, which contains the CD4/CD8 Vif (144-158) epitope, can boost Vif-specific CD8+ T cell responses after immunization with a plasmid encoding Vif (pVAX-Vif).

Methods

Synthetic genes encoding either 18 HIV-1 CD4+ T cell epitopes or HIV-1 Vif were subcloned in the pVAX vector to obtain pVAX-HIVBr18 and pVAX-vif. BALB/c mice were immunized with pVAX-vif (3 doses) or preimmunized with pVAX-HIVBr18 before receiving pVAX-vif (2 doses) every 2 weeks. T cell responses were assessed by IFN-gamma ELISPOT, Cytometric Bead Array, intracellular cytokine staining and CFSE based proliferation assay.

Results

Immunization with pVAX-vif induced proliferation of CD4+ and CD8+ T cells against different pooled Vif peptides. Preimmunization with pVAX-HIVBr18 enhanced the magnitude and breadth of the proliferative response of central and effector memory CD4+ and CD8+ T cells against Vif peptide pool 9, containing the homologous peptide, and, surprisingly, to Vif pools 2, 3 and 7, which did not contain the epitope. Moreover, preimmunization with pVAX-HIVBr18 also increased the number of CD4+ and CD8+ T cells producing TNF-α and IFN-gamma.

Conclusion

Our data suggest that preimmunization with a plasmid encoding CD4+ T cell epitopes induces proliferative and cytokine responses of CD4+ and CD8+ T cells to multiple Vif peptide pools, suggesting an epitope spreading mechanism.

Author information

Correspondence to SP Ribeiro.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://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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Ribeiro, S., Almeida, R., Rosa, D. et al. P19-44. Priming with a DNA vaccine enconding HIV CD4+ T cell epitopes enhances responses against subsequent immunization with plasmid encoding Vif. Retrovirology 6, P364 (2009). https://doi.org/10.1186/1742-4690-6-S3-P364

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Keywords

  • Cell Epitope
  • Intracellular Cytokine Staining
  • Cytometric Bead Array
  • Epitope Spreading
  • Plasmid Encode