1. A Randomised, Double-Blind, Controlled Vaccine Efficacy Trial of DNA/MVA ME-TRAP Against Malaria Infection in Gambian Adults.
- Author
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Moorthy, Vasee S., Imoukhuede, Egeruan B., Milligan, Paul, Bojang, Kalifa, Keating, Sheila, Kaye, Pauline, Pinder, Margaret, Gilbert, Sarah C., Walraven, Gijs, Greenwood, Brian M., and Hill, Adrian V. S.
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MALARIA , *VACCINES , *EPITOPES , *THROMBOSPONDINS , *T cells - Abstract
Many malaria vaccines are currently in development, although very few have been evaluated for efficacy in the field. Plasmodium falciparum multiple epitope (ME)-thrombospondin-related adhesion protein (TRAP) candidate vaccines are designed to potently induce effector T cells and so are a departure from earlier malaria vaccines evaluated in the field in terms of their mechanism of action. ME-TRAP vaccines encode a polyepitope string and the TRAP sporozoite antigen. Two vaccine vectors encoding ME-TRAP, plasmid DNA and modified vaccinia virus Ankara (MVA), when used sequentially in a prime-boost immunisation regime, induce high frequencies of effector T cells and partial protection, manifest as delay in time to parasitaemia, in a clinical challenge model. Methods and Findings A total of 372 Gambian men aged 15-45 y were randomised to receive either DNA ME-TRAP followed by MVA ME-TRAP or rabies vaccine (control). Of these men, 296 received three doses of vaccine timed to coincide with the beginning of the transmission season (141 in the DNA/MVA group and 155 in the rabies group) and were followed up. Volunteers were given sulphadoxine/pyrimethamine 2 wk before the final vaccination. Blood smears were collected weekly for 11 wk and whenever a volunteer developed symptoms compatible with malaria during the transmission season. The primary endpoint was time to first infection with asexual P. falciparum. Analysis was per protocol. DNA ME-TRAP and MVA ME-TRAP were safe and well-tolerated. Effector T cell responses to a non-vaccine strain of TRAP were 50-fold higher postvaccination in the malaria vaccine group than in the rabies vaccine group. Vaccine efficacy, adjusted for confounding factors, was 10.3% (95% confidence interval, 22% to + 34%; p = 0.49). Incidence of malaria infection decreased with increasing age and was associated with ethnicity. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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