Poly I:C and STING Agonist-primed DC Increase Lymphoid Tissue Polyfunctional HIV-1-specific CD8 T Cells and Limit CD4 T-cell Loss in BLT Mice

Effective function of CD8 T cells and enhanced innate activation of DCs in response to HIV-1 is linked to protective antiviral immunity in controllers. Manipulation of DC targeting the master regulator TANK-binding Kinase 1 (TBK1) might be useful to acquire controller-like properties. Here, we evaluated the impact of the combination of 2´3´-c´diAM(PS)2 and Poly I:C as potential adjuvants capable of potentiating DC´s abilities to induce polyfunctional HIV-1 specific CD8 T-cell responses in vitro and in vivo using a humanized BLT mouse model. Adjuvant combination enhanced TBK-1 phosphorylation and IL-12 and IFN-β expression on DC and increased their ability to activate polyfunctional HIV-1-specific CD8 T cells in vitro. Moreover, higher proportions of hBLT mice vaccinated with ADJ-DC exhibited less severe CD4 T-cell depletion following HIV-1 infection compared to control groups. This was associated with infiltration of CD8 T cells in the white pulp from the spleen, reduced spread of infected p24 cells to LN, and with preserved abilities of CD8 T cells from the spleen and blood of vaccinated animals to induce specific polyfunctional responses upon antigen stimulation. Therefore, priming of DC with PolyI:C and STING agonists might be useful for future HIV-1 vaccine studies.