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EUROMALVAC-2
MALARIA
Framework programme: 5
Project number:
QLK2-CT-2002-01197
EC contribution: € 3 700 044
Duration: 36 months
Type: RS
Starting date: 1 September 2002
Graphic element The Second Phase of a European Malaria Vaccine Development Consortium

Summary:

The EUROMALVAC2 consortium will develop malaria vaccines inducing protective antibody responses to Plasmodium falciparum bloodstage antigens, moving leading vaccine candidates towards GMP-production and clinical trial whilst validating second and third generation candidates in its malaria vaccine R&D 'pipeline '. The major projects within the EUROMALVAC2 work programme involve: a) an optimisation of synthesis of lead candidate malaria vaccines based on merozoite surface protein 1 (MSPl ) and the apical merozoite antigen 1 (AMAl ); b) production and testing of more parasitised erythrocyte membrane protein (PfEMP-l)-based vaccines; c) production and testing of new vaccine formulations based on the N-terminal Block 2 sequences of MSP1 and on other, less well characterised merozoite antigens; d) development of a transmission blocking vaccine based on gametocyte antigen Pfs48/45; e) strengthening of preclinical and clinical testing facilities.

Objectives:

EUROMALVAC1 has brought PfMSP119 and PfAMA1 vaccines close to clinical trial and has developed an experimental PfEMP1 vaccine. More second generation vaccines are now needed for clinical trials and accelerated development of an effective malaria vaccine. EUROMALVAC2's plan is to expand Europe's portfolio of vaccines inducing protective antibody responses to key malaria antigens, continuing to validate vaccine constructs in the pipeline while optimising the lead vaccines in preparation for their phase I trials. More 'first' generation PfEMP1 vaccines will be tested, as will a novel MSP1 Block 2 vaccine. Development and validation studies will be initiated for MSP 3-8 and a prototype transmission blocking vaccine will be made. Further development of pre-clinical and clinical trial facilities will be carried out.

Description:

1) Immunogenicity of MSP119 and AMA1 will be improved using adjuvants and modified antigen to increase inhibitory antibodies. a) Combined vaccines, initially fusing MSP1 with AMA1 will be tested. b) Structural analysis of merozoite surface molecules will be further developed. c) Other merozoite surface proteins will be added to the vaccine development pipeline. d) MSP1 N-terminal Block 2 vaccine development will be accelerated, testing hepatitis B core antigen vaccines and protein, DNA, and virus-like particle vaccines. e) Precise identification of protective epitopes on PFEMP1 molecules and their production as recombinant molecules will be carried out. f) Coordinated efforts to purify recombinant PfEMP1 in native antigenic conformation will be made. g) PfEMP1 vaccines inducing antibody-blocking cytoadhesion will be tested on Saimiri monkeys. h) Transmission-blocking vaccine development will be accelerated using the Pfs48/ 45 antigen. i) Stable vaccinia viruses expressing Pfs48/45 markers.
2) Develop auxotrophic Plasmodium parasites dependent upon an exogenous supply of uracil by targeted deletion of the cloned parasite ura 3 gene.
3) Rationally develop axenic culture of malaria parasites, based upon detailed measurements of the intracellular environment of the infected erythrocyte.
4) Develop genetically engineered Plasmodium that is growth impaired through a strategic reduction in its ability to produce protein.
5) Initiate a discussion about genetically engineered malaria parasites in Africa that will further debate the application of attenuated parasites and liase with similar fora in Europe.

Milestones and expected results:

The second phase of the EUROMALVAC consortium's activity will accelerate the progress of the first generation lead candidate vaccines to clinical trial within the next 36 months. The urgent need to expand development of the pipeline of second generation candidate vaccines will be addressed in order to develop an effective malaria vaccine capable of inducing protective antibody responses to blood-stage parasite antigens.

Coordinator:

David Arnot
The University of Edinburgh
Institute of Cell, Animal and Population Biology
EH9 3JT Edinburgh
United Kingdom
Tel: +44 131 650 8655
Fax: +44 131 650 8655
E-mail: d.e.arnot@ed.ac.uk

Partners:

Principal
Scientific
Participants
Official Address Other Information
2Jana McBrideICAPB
Ashworth Laboratories
The King’s Buildings
West Mains Road
UK-EH9 3JT Edinburgh
United Kingdom
+44 131 650 5494
+44 131 667 3210
j.mcbride@ed.ac.uk
3Tony HolderDivision of Parasitology
NIMR
The Ridgeway
Mill Hill
UK-NW7 1AA London
United Kingdom
+44 20 8959 3666 Ext: 2175
+44 20 8913 8593
aholder@nimr.mrc.ac.uk
4Thor TheanderCentre for Medical Parasitology
University of Copenhagen
Panum Building 24.2
Blegdamsvej 3
DK 2200 Copenhagen
Denmark
+45 35 327677
+45 35 327851
theander@biobase.dk
5Graham BentleyInstitut Pasteur
Unite d’Immunologie Structurale
25 Rue du Docteur Roux
FR-75724 Paris
France
+33 1 45 68 86 10
+33 1 45 68 86 39
bentley@pasteur.fr
6Odile Mercereau-PuijalonInstitut Pasteur
Unite d’Immunologie Moleculaire des Parasites
25 Rue du Docteur Roux
FR-75724 Paris
France
+33 1 45 68 86 23
+33 1 4613584
omp@pasteur.fr
7Shirley LongacreInstitut Pasteur
Department d’Immunologie
25 Rue du Docteur Roux
FR-75724 Paris
France
+33 1 40 61 35 49
+33 1 45 68 84 32
longacre@pasteur.fr
8Alan ThomasBiomedical Primate Research Centre
PO Box 3306
NL-2280 GJ Rijswijk
The Netherlands
+31 15 2842538
+31 15 2843986
thomas@bprc.nl
9Robert SauerweinUniversity Hospital
Faculty of Medical Sciences
PO Box 9101
NL-6500 HB Nijmegen
The Netherlands
+31 24 3610577
+31 24 3614666
r.sauerwein@nmb.azn.nl
10Mo KlinkertBernhard-Nocht-Institut für Tropenmedizin
- Tropenmedizinische Grundlagenforschung
Bernhard-Nocht-Strasse 74
DE-20359 Hamburg
Germany
+49 40 42818 301 (office)
+49 40 42818 482 (lab)
+49 40 42818 400
mo.klinkert@bni.uni-hamburg.de
11David ConwayLondon School of Hygiene and Tropical Medicine
Keppel Street
UK-WC1E 7HT London
United Kingdom
+44 20 7927 2331
+44 20 7636 8739
david.conway@lshtm.ac.uk
12Mats WahlgrenDepartment of Parasitology, Mycology and Environmental Microbiology
Swedish Institute for Infectious Disease Control
SE-17182 Solna
Sweden
+46 8 7287277
+46 8 310525
mats.wahlgren@smi.ki.se

 
 
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