Background: We previously developed a DNA vaccine and a recombinant Sendai virus (SeV) vector vaccine and showed their potential for inducing virus-specific cytotoxic CD8⁺ T cells (CTL) efficiently in macaque AIDS models. Recent preclinical AIDS vaccine trials including ours showed CTL-associated control of immunodeficiency virus replication during the early phase of infection in macaque acute AIDS models. However, we do not know if such CTL-based control may be maintained in the late phase.

Methods: Three (3) macaques were immunized with an env- and nef-deleted proviral SHIV DNA and 2 macaques received an SIVmac239 Gag-expressing SeV vector vaccine. All of them showed greatly reduced set-point viral loads compared to unvaccinated controls in the early phase after SIVmac239 challenge. By longitudinal analysis of these macaques after such partial control of primary SIV infections, we examined if or how the CTL-based control may be lost in the chronic phase.

Results: All the macaques maintained SIV-specific CD8⁺ T-cells even in the late phase, but some of them lost the control. In contrast, the loss of control was associated with preferential loss of SIV-specific CD4⁺ T-cells. Among them, one macaque with a dominant epitope (Mamu-A*01-restricted Gag CM9)-specific CD8⁺ T-cell responses showed loss of viremia control without virus mutation in the epitope region. The macaque lost virus-specific CD4⁺ T-cells with loss of the control and finally lost a differentiated, CD45RA⁺ subset of virus-specific CD8⁺ T-cells.

Conclusions: Our results indicate that maintenance of virus-specific CD8⁺ T-cells would not always lead to sustained control of immunodeficiency virus infections.