Cytotoxic T cell polyepitope vaccines delivered by ISCOMs

• Published in: Vaccine 2001-09, Vol.19 (32), p.4669-4675
• Main Authors: Le, Thuy T.T., Drane, Debbie, Malliaros, Jim, Cox, John C., Rothel, Linda, Pearse, Martin, Woodberry, Tonia, Gardner, Joy, Suhrbier, Andreas
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Biological and medical sciences; CD8 antigen; chromium; Cytotoxic T lymphocyte; Cytotoxicity, Immunologic; Enzyme-Linked Immunosorbent Assay; Epidemiology. Vaccinations; Epitopes - administration & dosage; Epitopes - chemistry; Epitopes - genetics; Epitopes - immunology; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; g-Interferon; General aspects; Genetic Vectors - administration & dosage; Genetic Vectors - immunology; Immunobiology; Immunodominant Epitopes - administration & dosage; Immunodominant Epitopes - chemistry; Immunodominant Epitopes - genetics; Immunodominant Epitopes - immunology; Infectious diseases; Interferon-gamma - metabolism; ISCOM; ISCOMs - administration & dosage; ISCOMs - immunology; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Medical sciences; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Peptides - administration & dosage; Peptides - chemical synthesis; Peptides - immunology; Polytope; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - metabolism; Vaccination; Vaccines, DNA - immunology; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - immunology
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/S0264-410X(01)00243-2

CD8 αβ cytotoxic T lymphocyte (CTL) polyepitope or polytope vaccines have traditionally been delivered using recombinant vector or DNA based delivery modalities. Here we show the delivery of polytope vaccines in the form of either synthetic polypeptides or recombinant polytope proteins by ImmunoStimulatory COMplexes (ISCOMs®). Induction of multiple protective CTL responses by these polytope-ISCOM formulations were comparable to viral vector or DNA based delivery modalities as assessed by IFNγ ELISpot, chromium release and viral challenge assays. Measurement of CTL responses specific for the different epitopes revealed immunodominance patterns, which were largely independent of the vaccine vector or the order of the epitopes in the polytope. ISCOMs thus emerge as a viable human delivery modality for protein-based polytope vaccines.