Poly(dG) oligo deoxynucleotide conjugated protein vaccine specifically targets skin APCs and induces robust T cell immunity in vivo. (APP3P.110)

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Abstract The efficacy of current vaccines results from the induction of protective antibodies. However we still lack efficacious vaccines against many infectious agents that require durable and protective T cell immunity. Efficient and selective delivery of antigen and adjuvant to APCs in vivo remains a critical challenge to vaccine design. To accomplish both of these goals with a single delivery strategy we have designed an antigen and adjuvant delivery platform based on simple and direct coupling of Poly(dG) oligo deoxynucleotides to protein antigens. Initially we found that immunization of naïve animals by direct injection of conjugates of Poly(dG) and Ovalbumin, Poly(dG)-OVA induces priming of specific CTL responses, differentiation of naïve CD4 T cells into Th1 cells, induction of specific memory T cell responses and generation of specific antibody responses, in a scavenger receptor-dependent manner. Applying this strategy to HIV, we immunized mice with conjugated Poly(dG)-Gag and demonstrated potent induction of Gag-specific CTL and Th1-biased CD4 T cells immune responses in vivo. Further, in human models we show that intradermal injection of Poly(dG)-antigen conjugates result in efficient uptake by human dermal DCs that acquire potent T cell stimulatory functions. Our data suggests that the Poly(dG)-protein conjugate vaccine platform can both selectively target antigens to skin APCs and function as an APC-directed adjuvant to induce broad based cellular and humoral immunity.