Poly(dG) conjugated protein immunization targets dendritic cells and induces T cell immunity in vivo. (P4528)

Abstract

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