Preservation of a subset of SIV-specific central memory CD4+ T cells correlates with control of viremia in SIVmac251 infected macaques

The identification of protective immune responses preventing progression towards AIDS is critical for the design of prophylactic and therapeutic vaccines against HIV infection. We study 3 cohorts of chronically SIV-infected macaques controlling viral replication for long periods of time. These animals were monitored for plasma viremia and the presence of SIV specific T-cell memory subsets using intracellular staining and 10-parameters flow cytometry. We found preservation of central memory T cells (CM), defined as CD3+ CD45RA- CD28+ in the 3 cohorts of 'controllers'. We also found that a subset of SIVgag-specific CD4+ CM cells was preserved in all the macaques with significant control of viremia, whereas this population was absent in macaques with progressive disease. Animals with progressive disease had increased CD8+T cell responses with effector memory (EM) phenotype. Our goal is to optimize DNA vaccination to induce the subset of SIV-specific CD4+ CM.

DNA vaccination using a mixture of SIV antigens and cytokine DNA as molecular adjuvants together with improved DNA delivery resulted in high and broad immune responses, including high levels of SIV specific CD4+ CM cells. Our results demonstrate that preservation of SIV-specific CD4+IFNgamma+ CM T cells in infected macaques correlate with control of viremia and lack of progression towards immunodeficiency; DNA vaccination approaches are able to recruit this subset of cells.