title: Gene gun intradermal DNA immunization followed by boosting with modified vaccinia virus Ankara: enhanced CD8+ T cell immunogenicity and protective efficacy in the influenza and malaria models.
abstract: In influenza and malaria, CD8+ T cells play an important role in protective immunity in mice. An immunization strategy consisting of DNA priming followed by boosting with recombinant modified vaccinia virus Ankara (MVA) induces complete protection, associated with high levels of CD8+ T cells, against Plasmodium berghei sporozoite challenge in mice. Intradermal delivery of DNA with a gene gun requires smaller amounts of DNA than intramuscular injection, in order to induce similar levels of immune responses. The present study compares both routes for the induction of specific CD8+ T cell responses and protection using different prime-boost immunization regimes in the influenza and the malaria models. In the DNA/MVA regime, equally high CD8+ T cell responses and levels of protection are achieved using ten times less DNA when delivered with a gene gun compared to intramuscular injection.
authors.affiliation: PowderJect Pharmaceuticals plc, 4 Robert Robinson Avenue, The Oxford Science Park, Oxford, UK. pilar.degano@ndm.ox.ac.uk
authors.forename: P
authors.initials: P
authors.lastname: Dégano
authors.forename: J
authors.initials: J
authors.lastname: Schneider
authors.forename: C M
authors.initials: CM
authors.lastname: Hannan
authors.forename: S C
authors.initials: SC
authors.lastname: Gilbert
authors.forename: A V
authors.initials: AV
authors.lastname: Hill
mesh_terms: D000818:Animals; D019470:Biolistics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016054:DNA, Protozoan / Q000008:administration & dosage / Q000235:genetics; D004279:DNA, Viral / Q000008:administration & dosage / Q000235:genetics; D005260:Female; D007117:Immunization, Secondary; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D008288:Malaria / Q000276:immunology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D010962:Plasmodium berghei / Q000276:immunology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics* / Q000276:immunology
chemical_list: D016054:DNA, Protozoan; D004279:DNA, Viral; D007252:Influenza Vaccines; D017780:Malaria Vaccines; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA