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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
A randomised, double-blind, controlled vaccine efficacy trial of DNA/MVA ME-TRAP against malaria infection in Gambian adults
PLoS Medicine, Volume 1, No. 2, Article e33, Year 2004
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Description
Background: 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. Conclusions: DNA/MVA heterologous prime-boost vaccination is safe and highly immunogenic for effector T cell induction in a malaria-endemic area. But despite having produced a substantial reduction in liver-stage parasites in challenge studies of non-immune volunteers, this first generation T cell-inducing vaccine was ineffective at reducing the natural infection rate in semi-immune African adults. © 2004 Moorthy et al.
Authors & Co-Authors
Moorthy, Vasee S.
Unknown Affiliation
Imoukhuede, Egeruan Babatunde
Unknown Affiliation
Milligan, Paul J.M.
Unknown Affiliation
Bojang, Kalifa A.
Unknown Affiliation
Keating, Sheila Marie
Unknown Affiliation
Kaye, Pauline
Unknown Affiliation
Pinder, Margaret
Unknown Affiliation
Gilbert, Sarah C.
Unknown Affiliation
Walraven, Gijs E.L.
Unknown Affiliation
Greenwood, Brian M.
Unknown Affiliation
Hill, Adrian V. S.
Unknown Affiliation
Statistics
Citations: 180
Authors: 11
Affiliations: 5
Identifiers
Doi:
10.1371/journal.pmed.0010033
ISSN:
15491277
e-ISSN:
15491676
Research Areas
Disability
Genetics And Genomics
Infectious Diseases
Study Design
Cohort Study
Participants Gender
Male