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Research programme

 


VacTrainees

State-of-the-art high-throughput technology combined with in vitro and in vivo analyses will be used to discover antigens and predict immunity. This will be used to design new vaccines which will be tested in tissue and mouse models, as well as in human patients. High-throughput technologies will not only monitor the efficacy but also the safety of newly developed vaccines. VacTrain focuses on new vaccines for human cytomegalovirus infection, influenza, tuberculosisS. aureus infectionLyme disease, and malaria.

 

 

VacTrain has 4 scientific Work Packages (WPs):


               • WP1 Transcriptional profiling

 

               • WP2 Discovery of antigens and prediction of immunity


               • WP3 Testing in models


               • WP4 Study of efficacy in humans
 

 


 

   

 

WP1 Transcriptional profiling    
 

WP1 integrates high-throughput gene expression profiling using microarrays and next generation sequencing (NGS) to monitor host responses to infectious pathogens, and vaccine efficacy and safety. The approach is used for tuberculosis (TB) and congenital cytomegalovirus (CMV) infections. For tuberculosis, these techniques will be applied to characterize host immune responses by comparing transcription profiles of Mycobacterium tuberculosis infected mice to healthy controls. For CMV infections, gene expression profiles of infected children that are able to clear the infection will be compared to those of children that remain infected and develop disease. These studies will provide biomarkers for prediction of disease outcome, and new targets for vaccine development. Partners involved: P1-Leiden University Medical Center, the Netherlands (TB and CMV experts) and P6-Max Planck institute for Molecular Genetics, Germany (NGS expert).

 

 


 

WP2 Discovery of antigens and prediction of immunity 
 

The research projects included in WP2 focus on the host immune responses triggered by infectious pathogens such as Mycobacterium tuberculosis, Staphylococcus aureus, Borreliosia sp., human cytomegalovirus and influenzavirus. To this aim, peripheral blood mononuclear cells, serum or immune cells of infected hosts as well as of immunized hosts will be collected.  The immunogenicity of (early) proteins selected from pathogens will be determined and the B- and T-cell immunity will be phenotyped and characterized in vitro and in vivo in order to discover antigens which will be used to develop new vaccines against these infectious pathogens. Within WP2 three academic partners collaborate with an industrial partner. Partners involved: P1-Leiden University Medical Center, the Netherlands (TB and CMV experts), P2-University of Oxford, UK (S. aureus expert), P3-Vlaams Institute for Biotechnology, Belgium (Influenza expert) and P8-Valneva Austria, Austria (LB expert).
 


 

WP3 Testing in models
 

WP3 investigates T-cell immunity in the influenza, Staphylococcus aureus, Plasmodium falciparum and human cytomegalovirus models for which a joined platform of T-cell-analytical tools will be available for all ESRs. Animal models and an ex vivo decidual organ culture will be used to study the biology of pathogens, T-cell immunity, vaccine antigen delivery as well as the efficacy of vaccines. In addition, novel formulations of multivalent vaccine antigens with different proprietary adjuvants and delivery systems will be evaluated. The expected outcome of this WP3 activity is a set of novel vaccine formulation that can be advanced in the clinic. Partners involved: P1-Leiden University Medical Center, the Netherlands (CMV expert), P2-University of Oxford, UK (P. falciparum expert), P3-Vlaams Institute for Biotechnology, Belgium (Influenza expert), P4-Hadassah University, Israel (CMV-decidual organ culture expert) and P7-Novartis, Italy (vaccine fomulation expert).
 


 

WP4 Study of efficacy in humans
 

In WP4, linear peptide epitopes will be identified for the development of synthetic vaccines against human cytomegalovirus. Epitopes inducing protective humoral (mediated by antibodies) immunity and epitopes inducing cellular (mediated by T-cells) immunity as well as host responses to them will be defined in detailed laboratory studies. Vaccine efficacy will be determined in a pharmacodynamic study. Recently validated biomarkers will be used as endpoints in randomised controlled trials. The results will be related to the titre of antibodies specific for gB of CMV, and to the T-cell responses made in the same patients. Partners involved: P5-University College London, UK (CMV-human trial expert).

 

Funded by the EU under the FP7 Marie Curie Action - Grant number: 316655
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