Flt3 ligand and conjugation to IL-1β 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 I 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 I T-cell and CTL responses to HIV-1 gag antigenic epitopes. (C) 2002 Elsevier Science Ltd. All rights reserved.