Figure 1. Two dendritic cell vaccines. Flynn et al. and Kastenmüller et al. outline contrasting strategies for triggering robust cellular immunity in vivo.

Flynn et al. immunized monkeys with an antibody against the dendritic cell (DC) protein lymphocyte antigen 75 (LY75; DEC-205) fused to a model antigen, HIV gag p24 [a(1)] plus poly-ICLC adjuvant [a(2)]. PolyICLC is a synthetic double-stranded RNA formulated together with polylysine and carboxymethylcellulose that induces activation of toll-like receptor 3 (TLR3). In vivo, the primary vaccine and adjuvant was taken up by DCs [a(3)], which were further stimulated by a boosting vaccination of an attenuated New York vaccinia virus engineered to express HIV proteins [a(4)]. The resulting activated DCs elicited a robust cytotoxic T lymphocyte (CTL) and T helper cell response against HIV compared with that seen in controls receiving conventional vaccination formulations and regimens [c].

Kastenmüller et al. vaccinated mice with an aggregate of a conjugate made up of the model antigen ovalbumin and the small molecule vaccine adjuvant resiquimod [b(1)], which engaged TLR7 and TLR8 [b(2)]. After a booster shot of the same formulation [b(3)], activated DCs led to a strong CTL and T helper cell response [c] against ovalbumin in vaccinated mice compared with in controls given soluble antigen.

Oncovir Inc. has Hiltonol poly-ICLC in Phase I and Phase II testing as an adjuvant to immunotherapy against HIV and a range of cancers. Celldex Therapeutics Inc. has rights from 3M Co. to use resiquimod as an adjuvant in DC vaccines.