title: Prime-boost immunization generates a high frequency, high-avidity CD8(+) cytotoxic T lymphocyte population.
abstract: Development and expansion of high-avidity T cell populations may be important for the success of immunization strategies against HIV and other pathogens that have presented major problems for vaccine development. We have used tetrameric-MHC complexes ex vivo and lytic assays to show that 'prime-boost' immunization with DNA vaccines and recombinant poxvirus vectors generates high frequencies of cytotoxic T lymphocytes (CTL) that recognize target cells expressing very low levels of specific antigen. These cells persist for at least 6 months at levels representing approximately 10% of the CD8(+) T cell population. Using a novel in vivo assay, we also found that prime-boost immunized animals were capable of eliminating target cells expressing 10- to 100-fold less immunogenic peptide than mice given either vector alone. In addition, viral challenge led to rapid expansion of CTL effectors in prime-boost groups, to levels representing >30% of total CD8(+) T cell numbers. Strategies that generate specific T cells of high avidity, optimizing early detection of infected cells, offer new hope for effective prophylaxis and immunotherapy.
authors.affiliation: John Curtin School of Medical Research, Australian National University, Canberra, ACT 2610, Australia.
authors.forename: Marie J
authors.initials: MJ
authors.lastname: Estcourt
authors.forename: Alistair J
authors.initials: AJ
authors.lastname: Ramsay
authors.forename: Andrew
authors.initials: A
authors.lastname: Brooks
authors.forename: Scott A
authors.initials: SA
authors.lastname: Thomson
authors.forename: Coralie J
authors.initials: CJ
authors.lastname: Medveckzy
authors.forename: Ian A
authors.initials: IA
authors.lastname: Ramshaw
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007117:Immunization, Secondary / Q000379:methods*; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology / Q000276:immunology; D019444:Vaccines, DNA; D014616:Vaccinia virus / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D009842:Oligopeptides; D019444:Vaccines, DNA