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TB VACCINE CLUSTER
TUBERCULOSIS
Framework programme: 5
Project number:
QLK2-CT-1999-01093
EC contribution: € 4 999 996
Duration: 36 months
Type: RS
Starting date: 1 February 2000
Website: http://www.pasteur.fr/EC_TBvaccine/
Graphic element A Cluster for Tuberculosis Vaccine Development
Keywords: Tuberculosis; vaccine; immunity; genomic; genetics

Summary:

Recent progress in the fields of mycobacterial genetics, vaccinology and immunology provide exciting new opportunities for development of improved vaccines for tuberculosis (TB). The most effective approach to translating these opportunities into products involves construction and comparative analysis of multiple vaccine candidates, and requires the concerted efforts of academic and industrial researchers. The Cluster for TB Vaccine Development provides a European approach to accelerated vaccine development based on an integrated, goal-orientated, strategy. The cluster combines innovative approaches to a generation of vaccine candidates with the establishment of standardised protocols for their pre-clinical evaluation, and fundamental research into immunological mechanisms and correlates of protection. The overall goal of the cluster is to bring one or more vaccine candidates from the laboratory to a stage suitable for initiation of clinical trials within three years. The availability of an effective vaccination strategy for TB control would have major impact on health and quality of life in the EU and worldwide.

Problem:

Tuberculosis remains a leading cause of morbidity and mortality worldwide, accounting for more human lives than any other single infectious disease. After decades of declining incidence, the number of infected individuals is increasing once again in developed as well as developing countries, with the spread of multidrug-resistant tuberculosis making treatment of the disease increasingly difficult. In spite of long lasting and well-conducted control programmes, the EU remains vulnerable to a spread of tuberculosis by immigration and travel from developing countries, and from countries that belonged to the former Soviet Union.

Aim:

The overall objective of the cluster is to establish a framework for preclinical development of novel tuberculosis vaccine candidates. The aim is to identify optimal strategies for a generation of vaccine candidates by comparing innovative approaches based on identification of novel protein antigens, characterisation of non-protein antigens that elicit T cell responses in man, and construction of live attenuated strains of mycobacteria. New vaccines will be compared alone and in combination with standardised experimental challenge models to identify candidates superior to the existing BCG vaccine. In parallel, the immunological mechanisms underlying vaccine-induced protection will be characterised in man and in experimental models. This information will be used to develop immunological tests for initial clinical assessment of new vaccines.

Expected results:

The project for the cluster is based on five interactive component projects. The first will focus on establishing a standardised protocol for pre-clinical assessment of vaccine candidates in a series of animal challenge models. Candidates that perform optimally in naive challenge models in mice and guinea pigs will be taken forward into screening in bovine and primate models. The second and third projects are directed towards the discovery of new vaccine candidates, which will subsequently feed into the pre-clinical screening programme established in Project 1. In Project 2, powerful new tools for genetic manipulation of mycobacteria and comparative genomic analysis will be used to construct a new generation of live attenuated mycobacterial vaccines. These will include recombinant BCG strains optimised for immunogenicity and safety, as well as M. tuberculosis strains lacking key virulence determinants. Project 3 will focus on novel non-protein antigens from mycobacteria that have recently been demonstrated to induce human T cell responses. Finally, participants in the fourth project will study the immunological mechanisms underlying the protective immune responses induced by the different vaccine candidates. Gene-knockout mice and recently developed techniques for accurate quantitative analysis of antigen-specific T cell subsets and cytokines will be used to identify immune mechanisms in experimental animals. This will identify immunological tests suitable for initial assessment of new vaccines in clinical trials.

Potential applications:

Results obtained through collaborative research developed during this project will enable the construction of new vaccine candidates against tuberculosis. Such candidates have been obtained. They will be used in phase 1 clinical trials in the very near future.

Coordinator:

Brigitte Gicquel
Institut Pasteur
Unité de Génétique Mycobactérienne
25, rue du Dr. Roux
75724 Paris Cedex 15
France
Tel: +33 1 45 68 88 28
Fax: +33 1 45 68 88 43
E-mail: bgicquel@pasteur.fr

Partners:

Principal
Scientific
Participants
Official Address Other Information
2Peter AndersenStatens Seruminstitut, Bacterial Vaccine Department
5, Artillerivej
DK-2300 Copenhagen S
Denmark
Tel: +45 32 683462
Fax: +45 32 683035
E-mail: pa@ssi.dk
3Gregory J. Bancroft and Neil G. StokerDepartment of Infectious and Tropical Sciences
London School of Hygiene and Tropical Medicine
Keppel Street
UK-WC1E 7HT London
United Kingdom
Tel: +44 171 927 2361
Fax: +44 171 323 5687
E-mail: Gregory.Bancroft@lshtm.ac.uk
Tel: +44 171 927 2425
Fax: +44 171 637 4314
E-mail: neil.stoker@lshtm.ac.uk
4Marc BonnevilleINSERM U463 Institut de Biologie
9, quai Moncousu
FR-44035 Nantes Cedex 01
France
Te ;: +33 2 40 08 47 47
Fax: +33 2 40 35 66 97
E-mail: bonnevil@mx.sante.univ-nantes.fr
5Erik BöttgerInstitut für Medizinische Mikrobiologie der Universität Zürich
Gloriastrasse 30/32, Postfach
CH-8028 Zurich
Switzerland
Tel: +41 1 634 2700
Fax: +41 1 634 4906
E-mail: boettger@immv.unizh.ch
6Stewart ColeUnité de Génétique Moléculaire
Institut Pasteur
25, rue du Roux
FR-75724 Paris Cedex 15
France
Tel: +33 1 45 68 84 46
Fax: +33 1 40 61 35 83
E-mail: stcole@pasteur.fr
7Jean Content and Kris HuygenInstitut Pasteur de Bruxelles
Department of Virology
Rue England 642
BE-1180 Brussels
Belgium
Tel: +32 2 373 3416
Fax: +32 2 373 3291
E-mail: jcontent@ben.vub.ac.be
Tel: +32 2 373 3370
Fax: +32 2 373 3367
E-mail: chuygen@ben.vub.ac.be
8Mamadou Daffe, Isabelle Maridonneau-Parini and Germain PuzoInstitut de Pharmacologie et de Biologie Structurale
CNRS
205, Route de Narbonne
FR-31077 Toulouse Cedex
France
Tel: +33 5 61 17 55 69
Fax: +33 5 61 17 59 94
E-mail: daffe@ipbs.fr
Tel: +33 5 61 17 54 58
Fax: +33 5 61 17 59 94
E-mail: maridono@ipbs.fr
Tel: +33 5 61 17 55 04
Fax: +33 5 61 17 55 05
E-mail: germain@ipbs.fr
9Wilfried DalemansSmithKline Beecham Biologicals
Rue de l’Institut, 89
BE-1330 Rixensart
Belgium
Tel: +32 2 656 8526
Fax: +32 2 656 8113
E-mail: wilfried.dalemans@sbbio.be
10Charles de TaisneAventis Pasteur S.A.
2, avenue Pont Pasteur
FR-Lyon Cedex 07
France
Tel: +33 4 37 37 71 18
Fax: +33 4 37 37 71 19
E-mail: charles.detaisne@aventis.com
11Gennaro De LiberoExperimental Immunolgy
Department of Research, University Hospital
P.O.Box 4031
Hebelstrasse, 7
CH-4031 Basel
Switzerland
Tel: +41 61 265 2327
Fax: +41 61 265 2350
E-mail: Gennaro.DeLibero@unibas.ch
12Jean-Jacques FourniéINSERM U 395, CHU Purpan
B.P. 3028
FR-31300 Toulouse
France
Tel: +33 5 61 74 83 64
Fax: +33 5 61 74 83 86
E-mail: fournie@purpan.inserm.fr
13Brigitte GicquelUnité de Génétique Mycobactérienne
Institut Pasteur
25, rue du Roux
FR-75724 Paris Cedex 15
France
Tel: +33 1 45 68 88 28
Fax: +33 1 45 68 88 43
E-mail: bgicquel@pasteur.fr
14Robert HewinsonTB Research Group
VLA Weybridge
Woodham Lane
UK-KT15 3N8Addlestone
United Kingdom
Tel: +44 1932 357811
Fax: +44 1932 347046
E-mail: ghewinson.cvl.wood@gtnet.gov.uk
15Adrian HillThe University of Oxford
Windmill Road
UK-0X3 9DU Oxford -
United Kingdom
Tel: +44 1865 222301
Fax: +44 1865 221921
E-mail: adrian.hill@well.ox.ac.uk
16Kris HuygenInstitut Pasteur du Brabant
Department of Virology
Rue Engeland 642
BE-1180 Brussels
Belgium
T: (+32) 2 373 3370
F: (+32) 2 373 3367
Email: chuygen@ben.vub.ac.be
17P.R. Jungblut, Kaufmann S.H.E and Baerbel Raupach (Hess)Max-Planck Institute for Infection Biology
Schumannstraße 21/22
DE-10117 Berlin
Germany
Tel: +49 30 2846 0510
Fax: +49 30 2846 0501
E-mail: jungblut@mpiib-berlin.mpg.de
Tel: +49 30 2846 0500/502
Fax: +49 30 2846 0501
E-mail: kaufmann@mpiib-berlin.mpg.de
Tel: +49 30 2846 0525
Fax: +49 30 2846 0501
E-mail: raupach@mpiib-berlin.mpg.de
18Camille LochtInstitut Pasteur de Lille
1, rue du Pr. Calmette
B.P. 245
FR-59019 Lille Cedex
France
Tel: +33 3 20 87 11 51/57
Fax: +33 3 20 87 11 58
E-mail: camille.locht@pasteur-lille.fr
19D. LowrieNational Institute Medical Research
The Ridgeway, Mill Hill
UK-NW7 1AA London
United Kingdom
Tel: +44 181 959 3666, Ext 2399
Fax +44 181 906 4477
E-mail: dlowrie@nimr.mrc.ac.uk
20Marina LuquinDepart. de Genetica i Microbiologia
Facultad de Ciencias, Universitat Autonoma de Barcelona
ES-08193 Bellaterra (Barcelona)
Spain
Tel: +34 93 5812 540
Fax: +34 93 5812 387
E-mail: Marina.Luquin@cc.uab.es
21Isabelle Maridonneau-PariniCentre National de la Recherche Scientifique
Institut de Pharmacologie et de Biologie Structurale
205, route de Narbonne
FR - 31077 Toulouse
France
T: (+33) 5 61 17 54 58
F: (+33) 5 61 17 59 94
Email: maridono@ipbs.fr
22Philip MarshHead of Microbial Pathogenicity
CAMR
Porton Down,
UK-SP4 0JG Salisbury
United Kingdom
Tel: +44 1980 612287
Fax: +44 1980 612731
E-mail: phil.marsh@camr.org.uk
23Carlos MartínFacultad de Medicina
Dpto Microbiologia y Salud Publica
Universidad de Zaragoza
C/Domingo Miral s/n
ES-50009 Zaragoza
Spain
Tel: +34 9 76 761759
Fax: +34 9 76 761664
E-mail: carlos@posta.unizar.es
24John Joe McFaddenSchool of Biological Sciences
University of Surrey
UK-GU2 7XH Guildford
United Kingdom
Tel: +44 1483 876494
Fax: +44 1483 300374
E-mail: j.mcfadden@surrey.ac.uk
25Eva MedinaGBF - Department of Microbial Pathogenicity and Vaccine Research
Division of Microbiology GFB
Mascheroder Weg 1
DE-38124 Braunschweig
Germany
Tel: +49 531 6181 558
Fax: +49 531 6181 411
E-mail: eme@gbf.de
26Rune NilsenUniversity of Bergen
Centre for International Health
Armauer Hansen Building, Haukeland Sykehus
NO-5021 Bergen
Norway
Tel: +47 559 74983
Fax: +47 559 74979
E-mail: rune.nilsen@cih.uib.no
27Tom H.M. OttenhoffDepartment of Immunohematology and Blood Transfusion
Building 1, L3-33, Leiden University Medical Center
Albinusdreef 2
NL-2333 ZA Leiden
The Netherlands
Tel: +31 71 526 5128 (secr), +31 71 526 3809 (office)
Fax: +31 71 521 6751;
E-mail: t.h.m.ottenhoff@lumc.nl
28Fabrizio PocciaInstitute for Infectious Diseases
‘Lazzaro Spallanzani’
Via Portuense, 292
IT-00149 Roma
Italy
Tel: +39 06 55 170430/409
Fax: +39 06 55 170430
E-mail: poccia@uniroma2.it
29John PollokVeterinary Sciences Division
DANI
Stoney Road, Stormont
UK-BT4 3SD Belfast
United Kingdom
Tel: +44 1232 525684
Fax: +44 1232 525745
E-mail: john.pollock@dardni.gov.uk
30Germain PuzoInstitut de Pharmacologie et de Biologie Structurale IPBS-CNRS
205, route de Narbonne
FR - 31077 Toulouse Cedex 04
France
T: (+33) 5 61 17 55 04
F: (+33) 5 61 17 55 05
Email: germain@ipbs.fr
31Baerbel Raupach (Hess)Max-Planck-Institut for Infection Biology
Department of Immunology
Schumannstraße 21/22
DE - 10117 Berlin
Germany
T: (+49) 30. 28460 525
F: (+49) 30 28 460.501
Email: raupach@mpiib-berlin.mpg.de
32Steffen StengerUniversität Erlangen-Nürnberg
Institut für Klin. Mikrobiologie, Immunologie und Hygiene
Wasserturmstraße 3, P.O.Box 2069
DE-91054 Erlangen
Germany
Tel: +49 131 8523 647
Fax: +49 9131 85 22 573
E-mail: steffen.stenger@mikrobio.med.uni-erlangen.de
33Neil G. StokerLondon School of Hygiene and Tropical Medicine
University of London
Keppel Street
UK - London WC1E 7HT
United Kingdom
T: (+44) 171 927 24 25
F: (+44) 171 637 43 14
Email: neil.stoker@lshtm.ac.uk
34Stefan B. SvensonSwedish Institute for Infectious
Disease Control
SE-171 82 Solna
Sweden
Tel: +46 89 13903
Fax: +46 90 7770 269
E-mail: stefan.svenson@vmm.slu.se
35Jelle E.R. TholeDepartment of Bacteriology
Institute for Animal Science and Health
Edelhertweg 15, P.O.Box 15
NL-8200 AB Lelystad
The Netherlands
Tel: +31 320 238152
Fax: +31 320 238153
E-mail: j.e.r.thole@id.wag-ur.nl
36Alan ThomasDepartment of Parasitology
Biomedical Primate Research Center
Lange Kleiweg 151
NL-2288 GJ Rijswijk
The Netherlands
Tel: +31 15 284 2538
Fax: +31 15 284 3986
E-mail: thomas@bprc.nl
37K.B. WalkerImmunology Division
BIBSC
Blanche Lane
UK-EN6 3QG Potters Bar
United Kingdom
Tel: +44 1707 654753 Ext.423
Fax: +44 1707 650223
E-mail: bwalker@nibsc.ac.uk
38Douglas YoungWright Fleming Institute
Department of Medical Microbiology
St. Mary's Hospital - Medical School
Norfolk Place
UK-W2 1PG London
United Kingdom
Tel: +44 171 594 3956
Fax: +44 171 262 6299
E-mail: d.young@ic.ac.uk

 
 
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