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 m ultiple 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, R T 956-964) that showed stable binding to the HLA-A2.1 molecule in an in vit ro binding assay were able to elicit a strong specific immune response in H LA-A2.1 transgenic mice when injected with IFA or Montanide((R)). The use o f 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 whe ther ID can be overcome by a combined injection of peptide loaded MS with d ifferent release patterns. Taken together, it seems feasible to induce a sp ecific CTL response in HLA-A2.1 transgenic mice against several HIV protein s using short synthetic peptides and human compatible adjuvants. (C) 2001 E lsevier Science Ltd. All rights reserved.