title: Treatment of cattle with DNA-encoded Flt3L and GM-CSF prior to immunization with Theileria parva candidate vaccine antigens induces CD4 and CD8 T cell IFN-γ responses but not CTL responses.
abstract: Theileria parva antigens recognized by cytotoxic T lymphocytes (CTLs) are prime vaccine candidates against East Coast fever in cattle. A strategy for enhancing induction of parasite-specific T cell responses by increasing recruitment and activation of dendritic cells (DCs) at the immunization site by administration of bovine Flt3L and GM-CSF prior to inoculation with DNA vaccine constructs and MVA boost was evaluated. Analysis of immune responses showed induction of significant T. parva-specific proliferation, and IFN-γ-secreting CD4(+) and CD8(+) T cell responses in immunized cattle. However, antigen-specific CTLs were not detected. Following lethal challenge, 5/12 immunized cattle survived by day 21, whereas all the negative controls had to be euthanized due to severe disease, indicating a protective effect of the vaccine (p<0.05). The study demonstrated the potential of this technology to elicit significant MHC class II and class I restricted IFN-γ-secreting CD4(+) and CD8(+) T cells to defined vaccine candidate antigens in a natural host, but also underscores the need to improve strategies for eliciting protective CTL responses.
authors.affiliation: International Livestock Research Institute, P. O. Box 30709, Nairobi 00100, Kenya.
authors.forename: Duncan M
authors.initials: DM
authors.lastname: Mwangi
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Honda
authors.forename: Simon P
authors.initials: SP
authors.lastname: Graham
authors.forename: Roger
authors.initials: R
authors.lastname: Pelle
authors.forename: Evans L N
authors.initials: EL
authors.lastname: Taracha
authors.forename: James
authors.initials: J
authors.lastname: Gachanja
authors.forename: John K
authors.initials: JK
authors.lastname: Nyanjui
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Bray
authors.forename: Guy H
authors.initials: GH
authors.lastname: Palmer
authors.forename: Wendy C
authors.initials: WC
authors.lastname: Brown
authors.forename: Waithaka
authors.initials: W
authors.lastname: Mwangi
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000953:Antigens, Protozoan / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002417:Cattle; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000008:administration & dosage; D016052:Protozoan Vaccines / Q000008:administration & dosage*; D011994:Recombinant Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D016797:Theileria parva / Q000276:immunology* / Q000472:pathogenicity; D013801:Theileriasis / Q000276:immunology / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000008:administration & dosage
chemical_list: D000276:Adjuvants, Immunologic; D000953:Antigens, Protozoan; D008565:Membrane Proteins; D016052:Protozoan Vaccines; D011994:Recombinant Proteins; D019444:Vaccines, DNA; C084881:flt3 ligand protein; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor