title: Effect of pre-existing cytotoxic T lymphocytes on therapeutic vaccines.
abstract: Therapeutic vaccines which aim to induce CD8(+) cytotoxic T lymphocyte (CTL) responses will often be required to perform in the presence of pre-existing CTL which recognize epitopes within the vaccine. Here we explore the ability of a viral vaccine vector presenting several co-dominant CTL epitopes to prime CTL responses in animals that have a pre-existing CTL response to one of the epitopes in the vaccine. The vaccine was usually capable of inducing multiple new responses, suggesting that immunodomination effects of pre-existing CTL may generally be minimal following vaccination. However, when large numbers of pre-existing CTL were present, a novel type of immune modulation was observed whereby (1) the vaccine failed to prime efficiently new CTL responses that were restricted by the same MHC gene as the pre-existing responses, and (2) vaccine-induced CTL responses restricted by other MHC genes were enhanced. These results may have implications for therapeutic multi-epitope vaccines for diseases like HIV and melanoma, which aim to broaden CTL responses.
authors.affiliation: Australian National Centre for International & Tropical Health & Nutrition, Queensland Institute of Medical Research and the University of Queensland, Royal Brisbane Hospital, Brisbane, Australia.
authors.forename: M A
authors.initials: MA
authors.lastname: Sherritt
authors.forename: J
authors.initials: J
authors.lastname: Gardner
authors.forename: S L
authors.initials: SL
authors.lastname: Elliott
authors.forename: C
authors.initials: C
authors.lastname: Schmidt
authors.forename: D
authors.initials: D
authors.lastname: Purdie
authors.forename: G
authors.initials: G
authors.lastname: Deliyannis
authors.forename: W R
authors.initials: WR
authors.lastname: Heath
authors.forename: A
authors.initials: A
authors.lastname: Suhrbier
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology* / Q000627:therapeutic use; D014777:Virus Diseases / Q000276:immunology / Q000517:prevention & control
chemical_list: D000939:Epitopes; D014765:Viral Vaccines