Thursday, April 28, 2011
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
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.