Potency of Cell-Mediated Immune Responses to Different Combined HIV-1 Immunogens in a Humanized Murine Model

Abstract

In this study, cell-mediated immune responses were evaluated in HLA-A2.1 mice that received polycistronic vector expressing HIV-1 gp120, gag and pol or single vectors expressing gp120 +gag/pol as well as recombinant structural proteins and adjuvants. Mice primed with the polycistronic DNA/CpG and boosted with the same regimen plus proteins induced a higher T-cell proliferative response to gp120. However, a very high frequency of IFN-gamma was detected in mice received the mixture of gp120 + gag/pol DNA constructs, recombinant proteins and CpG. We also measured specific CD8+T cells by intracellular cytokine staining and dimer assay in response to HIV-1 peptides specific for HLA-A2.1 in PBMCs without in vitro expansion. The group that received single gp120+gag/pol DNA constructs, recombinant proteins and CpG had a higher CD8+T cell response to the mixture of peptides in comparison with the other groups that received the polycistronic construct. The present study reveals an optimal combination of immunogens to increase immune responses against HIV-1.