title: Flt3 ligand enhances the immunogenicity of a gag-based HIV-1 vaccine.
abstract: Liposomes and Flt3 ligand (Flt3L), a ligand for the fms-like tyrosine kinase receptor Flt3/ FLK2, can augment the immune response to an HIV peptide vaccine. The HGP-30 peptide used in these studies is a synthetic peptide that corresponds to a highly conserved region of HIV-1 p17 gag (amino acids 86-115). Mice were immunized with HGP-30 or HGP-30 conjugated to keyhole limpet hemocyanin (KLH) and delayed-type hypersensitivity (DTH) responses, antibody (IgG) amount and antigen-specific proliferative responses by spleen cells were used to monitor the immune response. Daily injections of Flt3L prior to HGP-30 administration enhanced significantly an antigen-specific lymphocyte proliferation response when compared with Flt3L, HGP-30 alone or HGP-30 containing liposomes. Intravenous administration of HGP-30 was superior to intramuscular (i.m.) immunization for the induction of DTH responses. The HGP-30/KLH containing liposomes enhanced both DTH and antibody responses, while liposomes containing HGP-30 peptide elicited only T cell responses. In these studies, either Flt3L or liposomes increased DTH responses compared with the i.m. injection of the HGP-30 vaccine alone.
authors.affiliation: Laboratory of Transplantation Immunology, Department of Pathology/Microbiology, 985660 Nebraska Medical Center, Omaha, NE 68198-5660, USA.
authors.forename: V M
authors.initials: VM
authors.lastname: Pisarev
authors.forename: P
authors.initials: P
authors.lastname: Parajuli
authors.forename: R L
authors.initials: RL
authors.lastname: Mosley
authors.forename: J
authors.initials: J
authors.lastname: Sublet
authors.forename: L
authors.initials: L
authors.lastname: Kelsey
authors.forename: P S
authors.initials: PS
authors.lastname: Sarin
authors.forename: D H
authors.initials: DH
authors.lastname: Zimmerman
authors.forename: M D
authors.initials: MD
authors.lastname: Winship
authors.forename: J E
authors.initials: JE
authors.lastname: Talmadge
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D003713:Dendritic Cells / Q000502:physiology; D015683:Gene Products, gag / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood; D015488:HIV Antigens / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006968:Hypersensitivity, Delayed; D008081:Liposomes / Q000008:administration & dosage; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus
chemical_list: D016915:AIDS Vaccines; D015683:Gene Products, gag; D015483:HIV Antibodies; D015488:HIV Antigens; D008081:Liposomes; D008565:Membrane Proteins; D014764:Viral Proteins; C084881:flt3 ligand protein; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1