title: Enhanced CD8 T cell immunogenicity and protective efficacy in a mouse malaria model using a recombinant adenoviral vaccine in heterologous prime-boost immunisation regimes.
abstract: Recombinant replication-defective adenovirus expressing the CS gene from Plasmodium berghei (Ad-PbCS) was found to induce a strong CD8(+) T cell response after intra-dermal or -muscular immunisation. Boosting of an adenovirus-primed immune response with the replication-impaired poxvirus, modified vaccinia virus Ankara (MVA) led to enhanced immunogenicity and substantial protective efficacy. The recombinant adenoviral vaccine was capable of boosting to protective levels a CD8(+) T cell response primed by either a plasmid DNA vaccine, a recombinant Ty virus-like particle vaccine or recombinant MVA each expressing the same epitope or antigen. Complete protective efficacy after intradermal immunisation was observed with the adenovirus prime-MVA boost regime. This study identifies recombinant replication-defective adenovirus as an alternative to recombinant replication-defective poxviruses as boosting agents for the induction of strong protective CD8(+) T cell responses.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, OX3 7BN, Oxford, UK. sarah.gilbert@well.ox.ac.uk
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Gilbert
authors.forename: Jörg
authors.initials: J
authors.lastname: Schneider
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Hannan
authors.forename: Jiang Ting
authors.initials: JT
authors.lastname: Hu
authors.forename: Magdalena
authors.initials: M
authors.lastname: Plebanski
authors.forename: Robert
authors.initials: R
authors.lastname: Sinden
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D007117:Immunization, Secondary; D008288:Malaria / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019444:Vaccines, DNA / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics
chemical_list: D017780:Malaria Vaccines; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic