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162 Low Dose of IL-2 as an Adjuvant to an NYVAC-SIV-gag-pol-env-Based Vaccine Expands Preferentially Virus-Specific Dominant Epitopes and Decreases Proliferative Response to SIV p27 Gag and Env in SIVmac251-Infected Macaques
E. Tryniszewska1, J. Nacsa1, Z. Hel1, W.-P. Tsai1, L. Stevceva1, R. W. Parks1, M. Moniuszko1, M. Lewis2, K. Smith3, J. Tartaglia4, and G. Franchini*1
1NCI, Bethesda, MD, USA; 2SRI, Frederick, MD, USA; 3Cornell Univ., New York, NY, USA; and 4Aventis-Pasteur, Toronto, Canada
Background: We have modeled the immunogenicity and efficacy of highly attenuated poxvirus-based vaccine candidates in chronically SIVmac251-infected macaques treated with ART and IL-2.
Methods: Following infection with SIVmac251, macaques were treated with ART and vaccinated in the presence/absence of IL-2. Eleven macaques received the vaccine in the absence of IL-2, 14 macaques in the presence; 4 macaques (control) were mock vaccinated. In Mamu-A*01 positive macaques, the virus-specific CD8+ T-cell responses were measured by using Mamu-A*01 peptides or tetramers for the immunodominant Gag 181 and Tat 28 SIV peptides or by ELISPOT with Mamu-A*01-restricted subdominant SIV peptides. In the other macaques, overlapping peptides encompassing the SIVmac251 Gag, Env, Tat, Rev, and Nef proteins were used in an ELISPOT assay. Proliferative responses were measured using purified p27 Gag and Env proteins.
Results: Vaccination increased significantly the frequency of Gag 181 tetramer positive cells in the blood of the immunized macaques and this increase was significantly greater in the presence of IL-2. Surprisingly, a significant decrease in the proliferative response to p27 Gag and gp120 induced by vaccination was observed in the presence of IL-2. Although it remains unclear how IL-2 decreases the proliferative response induced by NYVAC-SIV, this effect was also observed in macaques that experienced viral rebound in the presence of IL-2.
Conclusions: How preferential expansion by IL-2 of virus-specific dominant CD8+ T-cell responses in conjunction with the suppression of virus-specific proliferative responses will influence viremia containment once ART is suspended may provide clues on the relative importance of these responses in controlling viral replication in the infected macaques.
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