Phase 1 evaluation of 3 highly immunogenic prime-boost regimens, including a 12-month reboosting vaccination, for malaria vaccination in Gambian men.

Conference item

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: Moorthy, V; Imoukhuede, E; Keating, S; Pinder, M; Webster, D

• Publication status: Published
• Host title: The Journal of infectious diseases
• Volume: 189
• Issue: 12
• Pages: 2213-2219
• Publication date: 2004-06-01
• Event location: United States
• DOI: 10.1086/421118
• EISSN: 1537-6613
• ISSN: 0022-1899
• Keywords: Male; Epitopes, T-Lymphocyte; Humans; Animals; T-Lymphocytes; Malaria Vaccines; Malaria, Falciparum; Middle Aged; Vaccination; Immunization, Secondary; Gambia; Immunization Schedule; Vaccines, DNA; Adolescent; Immunization; Vaccinia virus; Plasmodium falciparum; Adult; Protozoan Proteins; Interferon-gamma