Cytotoxic T cell polyepitope vaccines delivered by ISCOMs.
CD8 alphabeta 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(R)). Induction of multiple protective CTL responses by these polytope-ISCOM formulations were comparable to viral vector or DNA based delivery modalities as assessed by IFNgamma 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.
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Cooperative Research Centre for Vaccine Technology, Australian National Centre for International and Tropical Health and Nutrition, Queensland Institute of Medical Research and the University of Queensland, Post Office Royal Brisbane Hospital, Brisbane.
Drane
D
D
Malliaros
J
J
Cox
J C
JC
Rothel
L
L
Pearse
M
M
Woodberry
T
T
Gardner
J
J
Suhrbier
A
A
D000595:Amino Acid Sequence; D000818:Animals; D003602:Cytotoxicity, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology; D016882:ISCOMs / Q000008:administration & dosage* / Q000276:immunology; D016056:Immunodominant Epitopes / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage* / Q000276:immunology
D000939:Epitopes; D016882:ISCOMs; D016056:Immunodominant Epitopes; D010455:Peptides; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D007371:Interferon-gamma