Flt3-ligand as a vaccine adjuvant: Results in a study of Flt3-ligand plus tetanus toxoid immunization

Dendritic cells (DC) efficiently process and present antigens to the effector arm of the immune system, thereby stimulating immunity against antigens of both foreign and self origin. Administration of Flt3-ligand (FL) has been reported to increase dendritic cell (DC) numbers in mice and humans. As a result, FL has attracted interest as an adjuvant for vaccine immunotherapy. To investigate whether FL might increase the immune response to a model recall antigen, we administered FL 25 μg/kg/d subcutaneously to six healthy volunteers followed by a standard injection of intramuscular tetanus toxoid (TT). A control cohort of six healthy volunteers received tetanus toxoid alone. Compared to subjects who received only TT, subjects who received Flt3L and TT had greater TT-specific DTH reactivity. In contrast, FL did not augment peripheral blood mononuclear cell proliferative responses or antibody responses to TT. FL resulted in inconsistent TT-specific T cell responses as measured by interferon-gamma ELISPOT and cytokine flow cytometry. We conclude that while FL mobilization of DC may enhance in vivo immune responses to a known immunogenic recall antigen, there are inconsistent effects on immune response detected by in vitro assays. Further study will be required to determine which individuals might experience augmentation of the immune response with FL.