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Phase 1 Evaluation of 3 Highly Immunogenic Prime-Boost Regimens, including a 12-Month Reboosting Vaccination, for Malaria Vaccination in Gambian Men

Vasee S. Moorthy, Egeruan B. Imoukhuede, Sheila Keating, Margaret Pinder, Daniel Webster, Michael A. Skinner, Sarah C. Gilbert, Gijs Walraven and Adrian V. S. Hill
The Journal of Infectious Diseases
Vol. 189, No. 12 (Jun 15, 2004), pp. 2213-2219
Published by: Oxford University Press
Stable URL: http://www.jstor.org/stable/30077109
Page Count: 7
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Phase 1 Evaluation of 3 Highly Immunogenic Prime-Boost Regimens, including a 12-Month Reboosting Vaccination, for Malaria Vaccination in Gambian Men
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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 1.5 X 108 and 1 X 108 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.

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