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A cluster for tuberculosis vaccine development

Objective

The overall objective of the Cluster is to establish a framework for preclinical development of novel tuberculosis vaccine candidates. We aim to identify optimal strategies for 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 or in combination in 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. Integration of these activites, with the participation of the top academic and industrial researchers in Europe (Aventis Pasteur, SmithKline Beecham and the Statens Serum Institut), is essential for completion of the final goal of bringing one or more new vaccines to a stage suitable for clinical trials.
Brief description
The workplan for the Cluster is based on five interactive component
Projects. Project 1 will focus on establishment of a standardised protocol
for preclinical assessment of vaccine candidates in a series of animal challenge models. Protein antigens with known vaccine potential will be used for comparative evaluation of delivery systems based on novel adjuvants, DNA constructs, and attenuated viral vectors. Candidates that perform optimally in naive challenge models in mice and guinea pigs will be taken forward into screening in bovine and primate models. Projects 2 and 3 are directed towards discovery of new vaccine candidates which will subsequently feed into the preclinical screening programme established in Project 1. Participants in Project 2 will use powerful new tools for genetic manipulation of mycobacteria 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 following random transposon mutagenesis or predictions from bioinformatic and comparative genomic analysis. Project 3 will focus on novel non-protein antigens from mycobacteria that have recently been demonstrated to induce human T cell responses. A key aspect of the Cluster is that each of these strategies can be pursued simultaneously and that the different classes of candidate can be directly compared against each other and in combination. Finally, participants in Project 4 will study the mechanisms underlying the pathological manifestations of tuberculosis and the protective immune responses induced by the different vaccine candidates. This will identify immunological tests suitable for initial assessment of new vaccines in clinical trials.

Funding Scheme

CSC - Cost-sharing contracts
Leaflet | Map data © OpenStreetMap contributors, Credit: EC-GISCO, © EuroGeographics for the administrative boundaries

Coordinator

INSTITUT PASTEUR
Address
Rue Du Docteur Roux 25
75724 Paris
France

Participants (29)

AUTONOMOUS UNIVERSITY OF BARCELONA
Spain
Address
Campus Universitari Bellaterra
08193 Bellaterra
AVENTIS PASTEUR SA
France
Address
58,Avenue Pont Pasteur, 2
69007 Lyon
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE
France
Address
205,Route De Narbonne 205
31077 Toulouse
FOUNDATION BIOMEDICAL PRIMATE RESEARCH CENTRE
Netherlands
Address
151,Lange Kleiweg 151
2280 GH Rijswijk Zh
GBF - NATIONAL CENTRE FOR BIOTECHNOLOGY
Germany
Address
Mascheroder Weg 1
38124 Braunschweig
ID LELYSTAD - INSTITUTE FOR ANIMAL HEALTH AND SCIENCE
Netherlands
Address
Edelhertweg 15
8219 PH Lelystad
IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE
United Kingdom
Address
South Kensington Campus
London
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France
Address
Rue De Tolbiac, 101
75654 Paris
INSTITUT PASTEUR DE LILLE
France
Address
Rue Du Professeur Calmette 1
59019 Lille
INSTITUTE FOR INFECTIOUS DISEASES "LAZZARO SPALLANZANI"
Italy
Address
Via Portuense, 292
00149 Roma
LEIDEN UNIVERSITY
Netherlands
Address
2,Albinusdreef 2
2300 RC Leiden
LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE
MAX-PLANCK-GESELLSCHAFT ZUR FOERDERUNG DER WISSENSCHAFTEN E.V.
Germany
Address
Monbijoustrasse 2
10117 Berlin
MICROBIOLOGICAL RESEARCH AUTHORITY
United Kingdom
Address
Porton Down
SP4 0JG Salisbury
MINISTERE AUX AFFAIRES SOCIALES A LA SANTE PUBLIQUE ET A L'ENVIRONNEMENT
Belgium
Address
642,Rue Engeland 642
1180 Bruxelles
MRC National Institute for Medical Research
United Kingdom
Address
The Ridgeway Mill Hil
NW7 1AA London
NATIONAL BIOLOGICAL STANDARDS BOARD
United Kingdom
Address
Blanche Lane, South Mimms
Potters Bar
SMITHKLINE BEECHAM BIOLOGICALS S.A
Belgium
Address
89,Rue De L'institut 89
1330 Rixensart
STATENS SERUM INSTITUT
Denmark
Address
5,Artillerivej 5
2300 Koepenhagen
SWEDISH INSTITUTE FOR INFECTIOUS DISEASE CONTROL
Sweden
Address
Nobels Vaeg 18
Solna
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
United Kingdom
Address
John Radcliffe Hospital - Oxfordshire 5802
OX3 9DU Oxford/headington
THE MINISTER OF AGRICULTURE, FISHERIES AND FOOD
United Kingdom
Address
Wood Ham Lane, New Haw
KT15 3NB Addlestone
THE QUEEN'S UNIVERSITY OF BELFAST
United Kingdom
Address
Stoney Road , Stormont
BT4 3SD Belfast
THE ROYAL VETERINARY COLLEGE
United Kingdom
Address
Hawkshead Lane, North Mymms
AL9 7TA Welham Green,hatfieid
UNIVERSIDAD DE ZARAGOZA
Spain
Address
Pedro Cerbuna, 12
50009 Zaragoza
UNIVERSITAET BASEL
Switzerland
Address
Hebelstrasse 20
4031 Basel
UNIVERSITY OF ERLANGEN-NUREMBERG
Germany
Address
Egerlandstrasse 1
91058 Erlangen
UNIVERSITY OF ZURICH
Switzerland
Address
Gloriastrasse 30/32
8028 Zurich
University of Surrey
United Kingdom
Address

GU2 5XH Guildford