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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Synergistic DNA-MVA prime-boost vaccination regimes for malaria and tuberculosis
Vaccine, Volume 24, No. 21, Year 2006
Notification
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Description
T-cell-mediated responses against the liver-stage of Plasmodium falciparum are critical for protection in the human irradiated sporozoite model and several animal models. Heterologous prime-boost approaches, employing plasmid DNA and viral vector delivery of malarial DNA sequences, have proved particularly promising for maximising T-cell-mediated protection in animal models. The T-cell responses induced by this prime-boost regime, in animals and humans, are substantially greater than the sum of the responses induced by DNA or MVA vaccines used alone, leading to the term introduced here of "synergistic" prime-boost immunisation. The insert in our first generation clinical constructs is known as multiple epitope-thrombospondin-related adhesion protein (ME-TRAP). We have performed an extensive series of phase I/II trials evaluating various prime-boost combination regimens for delivery of ME-TRAP in over 500 malaria-naïve and malaria-exposed individuals. The three delivery vectors are DNA, modified vaccinia virus Ankara (MVA) and, more recently, fowlpox strain 9 (FP9). Administration was intra-epidermal and intramuscular for DNA and intradermal for MVA and FP9. Doses of DNA ranged from 4 μg to 2 mg. Doses of MVA were up to 1.5 × 108 plaque forming units (pfu) and of FP9, up to 1.0 × 108 pfu. Further trials employing bacille Calmette-Guérin (BCG) as the priming agent and MVA expressing antigen 85A of Mycobacterium tuberculosis as the boosting agent has extended the scope of synergistic prime-boost vaccination. In this review we summarise the safety, immunogenicity and efficacy results from these malaria and tuberculosis vaccine clinical trials. © 2005 Elsevier Ltd. All rights reserved.
Authors & Co-Authors
Gilbert, Sarah C.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Moorthy, Vasee S.
United Kingdom, Oxford
University of Oxford
Gambia, Banjul
Medical Research Council Laboratories Gambia
Andrews, Laura
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Pathan, Ansar Ahmed
United Kingdom, Oxford
University of Oxford
McConkey, Samuel J.
United Kingdom, Oxford
University of Oxford
Gambia, Banjul
Medical Research Council Laboratories Gambia
Vuola, Jenni M.
United Kingdom, Oxford
University of Oxford
Keating, Sheila Marie
United Kingdom, Oxford
University of Oxford
Berthoud, Tamara Katherine
United Kingdom, Oxford
University of Oxford
Webster, Daniel Peter
United Kingdom, Oxford
University of Oxford
McShane, Helen
United Kingdom, Oxford
University of Oxford
Hill, Adrian V. S.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
United Kingdom, Oxford
University of Oxford
Statistics
Citations: 117
Authors: 11
Affiliations: 3
Identifiers
Doi:
10.1016/j.vaccine.2005.08.048
ISSN:
0264410X
Research Areas
Genetics And Genomics
Infectious Diseases