title: Phase 1 evaluation of 3 highly immunogenic prime-boost regimens, including a 12-month reboosting vaccination, for malaria vaccination in Gambian men.
abstract: Successful vaccination against intracellular pathogens, including liver-stage Plasmodium falciparum, will require induction of strong antigen-specific T lymphocyte responses. The multiple epitope (ME)-thrombospondin-related adhesion protein (TRAP) construct includes CD8(+) and CD4(+) T cell epitopes from pre-erythrocytic P. falciparum antigens fused in-frame to the entire pre-erythrocytic antigen TRAP. Three carriers for this construct--plasmid DNA and 2 recombinant nonreplicating poxviruses (modified vaccinia virus Ankara [MVA] and fowlpox strain 9 [FP9])--were administered at 3-week intervals in a heterologous prime-boost combination to 29 Gambian men aged 18-45 years. Doses of DNA ME-TRAP, MVA ME-TRAP, and FP9 ME-TRAP were 2 mg and 1.5x10(8) and 1x10(8) plaque-forming units, respectively. DNA ME-TRAP was injected intramuscularly; MVA ME-TRAP and FP9 ME-TRAP were injected intradermally. There were no clinically relevant laboratory abnormalities and no severe or serious adverse events related to vaccination. DNA/MVA and FP9/MVA regimens were the most potent inducers of circulating effector T cells seen to date in sub-Saharan Africa. Twelve months after the final vaccination, a single booster vaccination expanded the effector T cell pool to a similar or higher magnitude than that after the primary vaccinations. These results highlight optimized combination regimens with general relevance to the development of vaccines targeting intracellular pathogens.
authors.affiliation: Medical Research Council Laboratories, Banjul, Gambia.
authors.forename: Vasee S
authors.initials: VS
authors.lastname: Moorthy
authors.forename: Egeruan B
authors.initials: EB
authors.lastname: Imoukhuede
authors.forename: Sheila
authors.initials: S
authors.lastname: Keating
authors.forename: Margaret
authors.initials: M
authors.lastname: Pinder
authors.forename: Daniel
authors.initials: D
authors.lastname: Webster
authors.forename: Michael A
authors.initials: MA
authors.lastname: Skinner
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Gilbert
authors.forename: Gijs
authors.initials: G
authors.lastname: Walraven
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005714:Gambia; D006801:Humans; D007114:Immunization; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000096:biosynthesis; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000276:immunology; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics
chemical_list: D018984:Epitopes, T-Lymphocyte; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D019444:Vaccines, DNA; C069428:thrombospondin-related adhesive protein, protozoan; D007371:Interferon-gamma