Flt3 ligand and conjugation to IL-1beta peptide as adjuvants for a type 1, T-cell response to an HIV p17 gag vaccine.
The adjuvant activity of Flt3 ligand (Flt3L) and conjugation to an interleukin (IL)-1beta bioactive fragment were compared, either alone or in combination, for their ability to induce T- and B-cell responses to the HGP-30 peptide sequence (amino acids 86-115 of human immunodeficiency virus (HIV) gag p17). The efficiency of HGP-30/IL-1beta conjugation, Flt3L administration or both as adjuvants was examined and all were found to augment similar levels of delayed type hypersensitivity (DTH) responses. In contrast, significant antigen (Ag)-specific types 1 and 2 T-cell ELISPOT responses were induced only by the combination of adjuvants. Further, in vitro sensitization with HGP-30 selectively increased Ag-specific, type 1 T-cell and cytotoxic T lymphocyte (CTL) responses to HGP-30-derived nonapeptide epitopes, while type 2 responses declined as measured in the ELISPOT assay. No serum antibodies to HGP-30 were induced unless HGP-30 was conjugated to keyhole-limpet hemocyanin. This suggests that a combination adjuvant strategy using Flt3L and conjugation to a biologically active IL-1beta fragment may be used to preferentially increase type 1 T-cell and CTL responses to HIV-1 gag antigenic epitopes.
Pisarev
Vladimir M
VM
Laboratory of Transplantation Immunology, Department of Pathology/Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-7660, USA. vpisarev@unmc.edu
Parajuli
Prahlad
P
Mosley
R Lee
RL
Chavez
Jennifer
J
Zimmerman
Daniel
D
Winship
Douglas
D
Talmadge
James E
JE
D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic; D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division; D003713:Dendritic Cells / Q000166:cytology; D005260:Female; D015488:HIV Antigens / Q000276:immunology*; D006433:Hemocyanins / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008565:Membrane Proteins / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology*; D054301:gag Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; C052407:HGP-30 peptide, Human immunodeficiency virus-1; D015488:HIV Antigens; D007375:Interleukin-1; D008565:Membrane Proteins; D010455:Peptides; D018074:Vaccines, Conjugate; C084881:flt3 ligand protein; D054301:gag Gene Products, Human Immunodeficiency Virus; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin