View All Abstracts for Session 30
161 Anti-Nef SIV DNA Vaccination of Macaques Induces Multi-Specific Anti-Nef T-Cell Responses and Protection against Challenge with SIVmac251
E. Bonnin, P. Lefèbvre, I. Couillin, F. Letourneur, J.-G. Guillet, and F. Martinon*
ICGM-INSERM, Paris, France
Background: CD8+ T lymphocytes play a key role in controlling viremia during HIV infection. However, by using the SIV-infected monkey animal model, it has been shown that the virus escaped the CTL responses when directed against a limited number of epitopes.
Methods: We sequenced the Nef gene from viruses included in the SIVmac251 primary isolate. We focused on the known T-cell-recognized regions and we selected 6 sequences reflecting the variability of Nef into this pathogenic isolate. These sequences were cloned in pCI vector, under CMV enhancer/promoter, and rhesus macaques were immunized with the mixture of the 6 plasmids. IFN-gamma secreting cells and CTL induced by these immunizations were studied from PBMC stimulated with Nef peptides.
Results: The results show that 3 out of 4 immunized macaques recognized several regions of Nef. The monkeys were then challenged by the intrarectal route with 10 AID50 of pathogenic SIVmac251. Monkeys recognizing several Nef epitopes showed undetectable or very low viral load in plasma and PBMC. However, control of viremia and partial protection was also observed with macaques immunized with the control pCI vector. No virus-specific T-cell and antibody responses were detected in these animals before challenge. The follow-up study of challenged macaques indicated that the total T-cell response decreased in the protected monkeys whereas it increased in nonprotected monkeys.
Conclusions: These results raised the question of whether the T-cell response is efficient in clearing the virus or is the mirror of the virus activity. These observations also suggested that mechanisms other than adaptive immunity might be efficient in vaccination.
Contact Author about this Abstract
