Multiple CD4 and CD8 T-cell activation parameters predict vaccine efficacy in vivo mediated by individual DC-activating agonists
MJP Welters, MS Bijker, SJF van den Eeden… - Vaccine, 2007 - Elsevier
MJP Welters, MS Bijker, SJF van den Eeden, KLMC Franken, CJM Melief, R Offringa…
Vaccine, 2007•ElsevierA systematic comparison of the immunostimulatory capacity of TLR 2, 3, 4, 5, 7 and 9
agonists and an agonistic CD40-specific antibody was performed in a single long peptide
vaccination model. All adjuvants activated DC in vitro but not all induced a strong functional
T-cell response in vivo. Optimal clonal CD8+ T-cell expansion depended on the capacity of
agonists to mature pro-inflammatory DC and the duration of their in vivo stimulatory effect.
Strong agonists promoted the induction of both antigen-specific IFNγ-producing CD4+ T …
agonists and an agonistic CD40-specific antibody was performed in a single long peptide
vaccination model. All adjuvants activated DC in vitro but not all induced a strong functional
T-cell response in vivo. Optimal clonal CD8+ T-cell expansion depended on the capacity of
agonists to mature pro-inflammatory DC and the duration of their in vivo stimulatory effect.
Strong agonists promoted the induction of both antigen-specific IFNγ-producing CD4+ T …
A systematic comparison of the immunostimulatory capacity of TLR 2, 3, 4, 5, 7 and 9 agonists and an agonistic CD40-specific antibody was performed in a single long peptide vaccination model. All adjuvants activated DC in vitro but not all induced a strong functional T-cell response in vivo. Optimal clonal CD8+ T-cell expansion depended on the capacity of agonists to mature pro-inflammatory DC and the duration of their in vivo stimulatory effect. Strong agonists promoted the induction of both antigen-specific IFNγ-producing CD4+ T-helper cells and high numbers of IFNγ producing CD8+ effector T-cells that killed target cells in vivo. Importantly, the capacity of an agonist to function as an adjuvant depended on the vaccine strategy used. Collectively, the multi-parameter system presented here can be used as a general road map to develop therapeutic vaccines.
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