Objective To evaluate, in different models, the ability of TRAP derived immunogens to elicit protective immunity against a challenge with Plasmodium sporozoites.Expected OutcomeIt is anticipated that these experiments will allow us to select an appropriate delivery system for TRAP derived immunogens inducing both humoral and cell mediated cytotoxic immunity. This information will provide the rationale for developing an experimental TRAP vaccine for human trials.* Selection of delivery systems for inducing humoral immunity and specific CTLs against TRAP. Few antigen delivery systems, have been shown to induce both humoral immunity and specific CTLs, these include: recombinant vaccinia viruses; lipidic adjuvants; naked DNA; listeriolysin O (LLO) of L. monocytogenes. We will compare the relative efficacy of these delivery systems to induce an appropriate immune response against P. berghei TRAP immunogens containing B cell, Helper and CTL epitopes. Cell lines will stably transfected with a series of DNA vectors inducing the expression of progressively deleted PbTRAP constructs.* Analysis of TRAP epitopes variability among P. falciparum isolates. Polymorphisms of immunologically relevant epitopes will render problematic the use of TRAP for the development of a vaccine. A total of one hundred blood samples will be collected from different locations of endemic areas in Mali at different time points during the malaria transmission season. Parasite DNA will be extracted from bloodspots and amplified with combinations of primers generating sequences of immunologically relevant T and B cell epitopes permitting direct DNA sequencing to look for mutations.* Cloning of TRAP homologues from P. knowlesi, P. cynomolgi and P. fragile. There are no perfect host systems that can be used to model P. falciparum infection in humans. Aotus and Saimiri genera are variably susceptible to blood stage infections from a limited range of adapted parasite species, a challenge model with Aotus is limited to the use of particular monkey subspecies (Aotus lemurinus) and to a particular parasite strain (P. falciparum St. Lucia). Specific PCR products will be generated from parasite DNA using primers for regions of TRAP that are conserved between the Plasmodium species. Labelled PCR products will be used as probes to screen lambda gt 10/lambda gt 11 genomic libraries developed from DNA of P. knowlesi, P. cynomolgi and P. fragile.* Evaluation of experimental induced PfTRAP immunity against Plasmodium sporozoite challenge. The TRAP gene from the St. Lucia strain will be amplified in PCR experiments, cloned and sequenced. A cohort consisting of 10 adult animals of either sex will be randomly assigned to three experimental groups of five animals each. The two groups of monkeys will be immunized with constructs generated using either St. Lucia TRAP or a polymorphic PfTRAP variant. After thorough analysis of humoral and cellular responses all the monkey cohorts will be challenged with 20,000 St. Lucia sporozoites. Monkeys will be observed daily for parasitemia. Fields of science medical and health scienceshealth sciencesinfectious diseasesmalarianatural sciencesbiological sciencesmicrobiologyvirologynatural sciencesbiological sciencesgeneticsDNAmedical and health sciencesbasic medicineimmunologymedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccines Programme(s) FP4-INCO - Specific research, technological development and demonstration programme in the field of cooperation with third countries and international organizations, 1994-1998 Topic(s) 03010302 - Research on the tools for prevention and the fight against the predominant diseases Call for proposal Data not available Funding Scheme CSC - Cost-sharing contracts Coordinator IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE EU contribution No data Address Campus at Silwood Park, Road A329 (Virginia Water SW7 2AZ LONDON United Kingdom See on map Total cost No data Participants (3) Sort alphabetically Sort by EU Contribution Expand all Collapse all Ecole Nationale de Médecine et de Pharmacie Mali EU contribution No data Address Point "G" 10 Bamako See on map Total cost No data FOUNDATION BIOMEDICAL PRIMATE RESEARCH CENTRE Netherlands EU contribution No data Address Lange Kleiweg 139 2288 GJ RIJSWIJK ZH See on map Total cost No data The Chancellor, Masters and Scholars of the University of Oxford United Kingdom EU contribution No data Address John Radcliffe Hospital Headington OX3 9DU Oxford See on map Total cost No data
