Preserved CD4+ Central Memory T Cells and Survival in Vaccinated SIV-Challenged Monkeys

Abstract

Vaccine-induced cellular immunity controls virus replication in simian immunodeficiency virus (SIV)-infected monkeys only transiently, leading to the question of whether such vaccines for AIDS will be effective. We immunized monkeys with plasmid DNA and replication-defective adenoviral vectors encoding SIV proteins and then challenged them with pathogenic SIV. Although these monkeys demonstrated a reduction in viremia restricted to the early phase of SIV infection, they showed a prolonged survival. This survival was associated with preserved central memory CD4 + T lymphocytes and could be predicted by the magnitude of the vaccine-induced cellular immune response. These immune correlates of vaccine efficacy should guide the evaluation of AIDS vaccines in humans.

Partial protection against SIV challenge by vaccination of adenovirus and MVA vectors in rhesus monkeys

“…This was previously shown to correlate with survival in SIVinfected monkeys. 13,23 Vaccination induced both anti-SIVgag-and antiSIVenv-specific Ab production (Figures 7 and 8). Like any other current HIV vaccine, this vaccine may not be expected to elicit humoral immune responses that can broadly neutralize HIV/SIV isolates for a prolonged period of time.…”

“…The data obtained from this study show that the vaccination failed to control SIV replication completely, but prevented CM CD4 T-cell loss to a remarkable extent, which may greatly influence disease progression. 23 …”

“…50,51 The memory CD4 T cells that survive the initial virusmediated purge may subsequently expand, and several studies have suggested that prophylactic vaccination may help preserve and maintain these memory CD4 T cells. 13,23,52 Numerous studies have verified the importance of CM CD4 T cells in suppressing viral replication and mortality after viral infections. 13,23,46 In the current study, memory CD4 T cells were present in the PBMC before and after SIV infection.…”

“…13,23,52 Numerous studies have verified the importance of CM CD4 T cells in suppressing viral replication and mortality after viral infections. 13,23,46 In the current study, memory CD4 T cells were present in the PBMC before and after SIV infection. After SIV infection, no significant difference was observed in the number of naive CD4 T cells and EM CD4 T cells between the vaccine and control groups ( Figure 5).…”

“…Naive CD4 T cells, EM CD4 T cells and CM CD4 T cells were identified as CD3 + CD4 + CD95 À CD28 + , CD3 + CD4 + CD95 + CD28 À and CD3 + CD4 + CD95 + CD28 + , respectively. 13,23,46 Tetramer assay…”