title: The use of Flt3 ligand as an adjuvant for hepatitis B vaccination of healthy adults.
abstract: A phase I/II clinical trial was carried out to determine the safety of Flt3 ligand used as a vaccine adjuvant when administered to healthy human volunteers on two different schedules. In the first phase of this study, Flt3 ligand was administered SQ at a dose of 20 microg/kg (to a maximum of 1500 microg) every day (N=10) or every other day (N=10) for 1 week. The Flt3 ligand injection series was followed 1 day later by the first of three vaccinations with the licensed hepatitis B vaccine. In the second phase of the trial, 30 volunteers received either Flt3 ligand or placebo on the alternate day schedule in a randomized, double-blind design. The Flt3 ligand injections were safe and very well-tolerated. The number of lineage negative, HLA-DR(hi), CD11c(+), CD123(-) dendritic cells (DCs) increased 23-fold, and the lineage negative, HLA-DR(hi), CD11c(-), CD(123 bright) pre-DCs increased 6-fold. There was an associated increase in monocytes and WBCs in the Flt3 ligand recipients. Despite the marked increase in peripheral circulating dendritic cells, no increase was observed in the hepatitis B antibody titers induced after vaccination.
authors.affiliation: Division of Infectious Diseases, University of California, Davis, PSSB, Suite 500, 4150 V St, Sacramento, CA 95817, USA. tgevans@ucdavis.edu
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Evans
authors.forename: Muhammad
authors.initials: M
authors.lastname: Hasan
authors.forename: Laurent
authors.initials: L
authors.lastname: Galibert
authors.forename: Dania
authors.initials: D
authors.lastname: Caron
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D006510:Hepatitis B Antibodies / Q000097:blood*; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000008:administration & dosage / Q000276:immunology*; D012449:Safety; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D008565:Membrane Proteins; C084881:flt3 ligand protein