title: Prime boost vaccination strategies: CD8 T cell numbers, protection, and Th1 bias.
abstract: Vaccination strategies involving priming with DNA and boosting with a poxvirus vector have emerged as a preferred combination for the induction of protective CD8 T cell immunity. Using IFN-gamma ELISPOT and a series of DNA plasmid, peptide, and modified vaccinia Ankara (MVA) vaccine combinations, we demonstrate that the DNA/MVA combination was uniquely able to enhance IFN-gamma secretion by Ag-specific CD8 T cells. However, CD8 T cell populations induced by DNA/MVA vaccination failed to show an enhanced capability to mediate protection in an IFN-gamma-independent influenza challenge model. The DNA/MVA vaccine strategy was also not unique in its ability to induce high numbers of CD8 T cells, with optimal strategies simply requiring the use of vaccine modalities that individually induce high numbers of CD8 T cells. These experiments argue that rivals to DNA/poxvirus vaccination strategies for the induction of optimal protective CD8 T cell responses are likely to emerge.
authors.affiliation: Queensland Institute of Medical Research, Cooperative Research Center for Vaccine Technology, Australian Center for International & Tropical Health & Nutrition, Brisbane, Australia.
authors.forename: Tonia
authors.initials: T
authors.lastname: Woodberry
authors.forename: Joy
authors.initials: J
authors.lastname: Gardner
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Elliott
authors.forename: Sonja
authors.initials: S
authors.lastname: Leyrer
authors.forename: David M
authors.initials: DM
authors.lastname: Purdie
authors.forename: Paul
authors.initials: P
authors.lastname: Chaplin
authors.forename: Andreas
authors.initials: A
authors.lastname: Suhrbier
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D005260:Female; D005822:Genetic Vectors / Q000276:immunology; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods*; D009980:Influenza A virus / Q000254:growth & development / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology / Q000821:virology; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
chemical_list: D007252:Influenza Vaccines; D019444:Vaccines, DNA; D007371:Interferon-gamma