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A cluster for tuberculosis vaccine development

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.

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Coordinator

INSTITUT PASTEUR

Address

Rue Du Docteur Roux 25
75724 Paris

France

Administrative Contact

Jean CASTEX

Participants (29)

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AUTONOMOUS UNIVERSITY OF BARCELONA

Spain

AVENTIS PASTEUR SA

France

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE

France

FOUNDATION BIOMEDICAL PRIMATE RESEARCH CENTRE

Netherlands

GBF - NATIONAL CENTRE FOR BIOTECHNOLOGY

Germany

ID LELYSTAD - INSTITUTE FOR ANIMAL HEALTH AND SCIENCE

Netherlands

IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE

United Kingdom

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE

France

INSTITUT PASTEUR DE LILLE

France

INSTITUTE FOR INFECTIOUS DISEASES "LAZZARO SPALLANZANI"

Italy

LEIDEN UNIVERSITY

Netherlands

LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE

MAX-PLANCK-GESELLSCHAFT ZUR FOERDERUNG DER WISSENSCHAFTEN E.V.

Germany

MICROBIOLOGICAL RESEARCH AUTHORITY

United Kingdom

MINISTERE AUX AFFAIRES SOCIALES A LA SANTE PUBLIQUE ET A L'ENVIRONNEMENT

Belgium

MRC National Institute for Medical Research

United Kingdom

NATIONAL BIOLOGICAL STANDARDS BOARD

United Kingdom

SMITHKLINE BEECHAM BIOLOGICALS S.A

Belgium

STATENS SERUM INSTITUT

Denmark

SWEDISH INSTITUTE FOR INFECTIOUS DISEASE CONTROL

Sweden

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD

United Kingdom

THE MINISTER OF AGRICULTURE, FISHERIES AND FOOD

United Kingdom

THE QUEEN'S UNIVERSITY OF BELFAST

United Kingdom

THE ROYAL VETERINARY COLLEGE

United Kingdom

UNIVERSIDAD DE ZARAGOZA

Spain

UNIVERSITAET BASEL

Switzerland

UNIVERSITY OF ERLANGEN-NUREMBERG

Germany

UNIVERSITY OF ZURICH

Switzerland

University of Surrey

United Kingdom

Project information

Grant agreement ID: QLK2-CT-1999-01093

  • Start date

    1 February 2000

  • End date

    31 January 2004

Funded under:

FP5-LIFE QUALITY

  • Overall budget:

    € 7 742 285

  • EU contribution

    € 4 914 917

Coordinated by:

INSTITUT PASTEUR

France