Induction of a cytotoxic T-cell response to HIV-1 proteins with short synthetic peptides and human compatible adjuvants.
The goal of this study was the induction of a strong CTL response against multiple CTL epitopes present in HIV proteins using short synthetic peptides. Four HLA-A2.1 restricted peptides (RT 476-484, p17 77-85, gp41 814-823, RT 956-964) that showed stable binding to the HLA-A2.1 molecule in an in vitro binding assay were able to elicit a strong specific immune response in HLA-A2.1 transgenic mice when injected with IFA or Montanide. The use of biodegradable microspheres (MS) as adjuvant was also successfully tested for all peptides. When the peptides were injected as a mixture the response was weaker as compared to individual injections of the peptides indicating the occurrence of immunodominance (ID). We are currently investigating whether ID can be overcome by a combined injection of peptide loaded MS with different release patterns. Taken together, it seems feasible to induce a specific CTL response in HLA-A2.1 transgenic mice against several HIV proteins using short synthetic peptides and human compatible adjuvants.
Peter
K
K
Institute of Biochemistry, University of Lausanne, Chemin des Boveresses 155, 1066, Epalinges, Switzerland.
Men
Y
Y
Pantaleo
G
G
Gander
B
B
Corradin
G
G
D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D005260:Female; D015497:HIV-1 / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000502:physiology*; D006801:Humans; D007114:Immunization; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008863:Microspheres; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D015789:HLA-A2 Antigen; D010446:Peptide Fragments