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Development of tuberculosis vaccine with consistent efficacy in differentregions of the world

Objective

* To construct and investigate the efficacy and mode of action of experimental vaccines in animal models.
* To study the interactions between environmental mycobacteria and vaccine induced protection in animal models.
Expected Outcome

An identification and recombinant production of novel immunodominant antigens. An overview of the immunogenicity and protective efficacy of these. An overview of the mycobacterial antigens that are relevant for protective immunity against tuberculosis in humans

2) Investigation of experimental vaccines in animal models

Objectives
* To construct and investigate the efficacy and mode of action of experimental vaccines in animal models.
* To study the interactions between environmental mycobacteria and vaccine induced protection in animal models.

Activities
Production of a fusion protein consisting of ESAT-6 and Ag85B. Testing of the immunogenicity of this hybrid molecule. The level of acquired resistance following immunization with the hybrid in the presence or absence of various cytokines and inhibitors will be studied. The influence of pre-vaccination exposure to environmental mycobacteria on immune responses as well as BCG replication will be monitored and the influence on subsequent protection against tuberculosis evaluated.

Expected outcome
Characterization of the mechanisms underlying the vaccine induced protective immunity. Information on the interaction between immunization and
sensitization with environmental mycobacteria.

3) Production of ST-CF/DDA vaccine for human use

Objectives
* To produce and test the new ST-CF/DDA vaccine in humans.
Production of an extensive panel of recombinant Culture Filtrate Proteins (CFPs) from cultures of virulent M. tuberculosis. Characterization of the antigens expressed by environmental mycobacteria isolated from the Karonga District in Malawi. Investigation of the recognition of these antigens i) in vitro by cells from memory immune mice and recently infected mice, ii) in vitro by defined groups of TB infected, BCG vaccinated, and unimmunized human donors, and iii) in vivo by guinea pigs (skintest). The protective efficacy of the antigens alone or in combination will finally be evaluated in mice and guinea pigs.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

STATENS SERUM INSTITUT
Address
5,Artillerivej 5
2300 Koepenhagen
Denmark

Participants (5)

ARMAUER HANSEN RESEARCH INSTITUTE
Ethiopia
Address
1005
2003 Addis Abeba
LEPRA Malawi - Leprosy Relief Association
Malawi
Address

10 Chilumba
National Institute of Public Health
Norway
Address
75,Geitmyrsveien
0462 Oslo
Universidade do Porto
Portugal
Address
823,Rua Do Campo Alegre
4150 Porto
University of Oslo
Norway
Address

0027 Oslo