Flt3 ligand and conjugation to IL-1β peptide as adjuvants for a type 1, T-cell response to an HIV p17 gag vaccine

Vladimir M. Pisarev, Prahlad Parajuli, R. Lee Mosley, Jennifer Chavez, Daniel Zimmerman, Douglas Winship, James E. Talmadge

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

The adjuvant activity of Flt3 ligand (Flt3L) and conjugation to an interleukin (IL)-1β 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-1β 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-1β fragment may be used to preferentially increase type 1 T-cell and CTL responses to HIV-1 gag antigenic epitopes.

Original languageEnglish (US)
Pages (from-to)2358-2368
Number of pages11
JournalVaccine
Volume20
Issue number17-18
DOIs
StatePublished - May 22 2002

Keywords

  • Flt3 ligand
  • Gag
  • IL-1β fragment
  • Peptide conjugates
  • Vaccine

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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