Objective To optimize the immunogenicity of MSP3 and GLURP by using several antigen-presentation systems in a) mice, b) Saimiri, c) Aotus, and d) Chimpanzee. To characterize the antibodies (fine epitope specificity, isotype) induced by the various protocols, and analyze their biological effect in defence mechanisms, a) in vitro, invasion and ADCI, b) in vivo by passive transfer in the humanized SCID mouse and in c) primate. Compare the results with P. falciparum challenge experiments in the primates immunized with MSP3 and GLURP. Complete the characterization of the B and T cell epitopes from MSP3 and GLURP by epidemiological field studies.Expected OutcomeThe optimal conditions for inducing antibodies against MSP3 and GLURP will be determined and functional protection assays established. Improved understand of the critical epitopes involved in the production of protective antibodies and cross-reactivity to MSP3 and GLURP.* Immunizing mice with one lipopeptide, and one recombinant from MSP3 and one peptide and one recombinant derived from GLURP with the different adjuvants. The titer, and isotype as well as the ADCI effect of the antibodies obtained will be determined.* Aotus will be BCG primed, immunized with PPD-coupled GLURP and MSP3 and subsequently challenged with P. falciparum.* ADCI experiments will be conducted in SCID mice harbouring live P. falciparum and human monocytes by passively transferring total IgG from hyperimmune individuals to confirm the model. Anti-R0, anti-R2, and anti-MSP3 and other antibodies will subsequently be analyzed in the SCID model.* Epidemiological studies with MSP3b and R0, and R2 in Dielmo.* Mice will be immunized with new peptides and recombinant proteins derived from MSP3 and GLURP with the best performing adjuvant. The titer, and isotype and ADCI effect of the antibodies induced by new constructs will be determined.* Immunizing Aotus and Saimiri with the GLURP and MSP3 vaccine formulation that induced antibodies which prove to be efficient in ADCI. The humoral and cellular immune responses of the monkeys will be analyzed.* The antibody reactivity to epitopes identified in MSP3 clone 256 and 256B and peptides derived from GLURP will be analyzed in the population of Dielmo.* Immunizing Aotus and Saimiri with antigens provided that they are superior to the initial constructs. The immunogenicity of the best performing MSP3 and GLURP antigen formulation will be determined in Chimpanzees. Fields of science natural sciencesbiological scienceszoologymammalogyprimatologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical 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 Statens Serum Institut EU contribution No data Address 5,Artillerivej 5 2300 København S Denmark See on map Total cost No data Participants (4) Sort alphabetically Sort by EU Contribution Expand all Collapse all INSTITUT PASTEUR France EU contribution No data Address Rue du Docteur Roux 28 75724 PARIS See on map Total cost No data Institut Pasteur de Lille France EU contribution No data Address 1 rue du Professeur Albert Calmette 59019 Lille See on map Total cost No data Oswaldo Cruz Institute Brazil EU contribution No data Address 4365,Av Brasil 4365 21045 Rio de Janeiro See on map Total cost No data UNIVERSIDAD DEL VALLE Colombia EU contribution No data Address 0344406 CALI See on map Total cost No data
