Objectif
The concept behind the proposal is the optimal design of anti-viral and anti-parasite vaccines. The strategy is to vaccinate with minimal structures consisting of rationally designed protective epitopes, adequately presented and easy to deliver, which are capable of stimulating effective B-cell, T-cell and cytotoxic immune responses whilst avoiding potentially hazardous and undesirable effects. The objective is to achieve vaccines which will be effective when delivered via the mucosal route and effective in the presence of maternal antibodies.
The precise objective is to develop second generation vaccines that will be more efficient, more economical, safer and easier to deliver than currently available vaccines. This will be achieved by using synthetic peptides, mimotopes, retro-inverso peptides, synthetic recombinant constructs and DNA vaccines. Molecular modelling will be used for the design of epitopes with the maximum binding affinity for MHC molecules on antigen-presenting cells and for antibodies. The cumulative data will be analysed to identify the optimal procedure(s) to provide the most efficient vaccines against the viral, bacterial or parasitic diseases under study. The conclusions arising from the work will be applicable for the design of vaccines against other pathogens.
Essentially all of the currently available vaccines are based on the use of inactivated or live-attenuated pathogens.
However, these vaccines have several shortcomings, such as difficulties of in-vitro culturing, biohazard risks, as well as loss of efficacy due to the genetic variations seen in many viruses. These problems can be solved by the work proposed here since the use of synthetic materials for vaccine production (available in unlimited quantities and posing no biohazard) and the use of a mixture of defined epitopes will lead to an effective broad range immune response which has the potential to overcome both strain specificity of the pathogen and the MHC restriction of the host.
Each of the partners in the proposal currently employs a different approach to vaccine development and uses a different pathogen. Hence in each laboratory, information can only be obtained on the efficacy of the particular approach and pathogens concerned and cannot provide comparisons with the other approaches or pathogens.
Each partner will use their unique expertise to prepare the vaccines according to his/her approach for all the biological systems of the other partners. Concomitantly, all the partners will test in their own system(s) the vaccines prepared by the other partners in comparison to their own.
The innovation in the proposal is that for the first time, a concerted effort will be made to compare different approaches for the design and synthesis of epitope-based vaccines and will provide completely new information on the comparative advantage of each of the approaches which are currently in use. Each partner will: a) propose the epitope(s) to be evaluated and molecular modelling will be used to improve the efficacy of MHC and antibody binding of epitopes identified by other technologies; b) prepare vaccines using their own expertise expressing epitopes of all other laboratories and provide the others with materials for immunisation in their respective biological systems; and c) evaluate the immune response and protective ability of the various vaccines expressing their own epitopes in the mouse model of infection.
If clear-cut advantage is demonstrated for one or more of the approaches, this particular vaccine will be investigated in an animal model more relevant to humans such as SCID huPBL mice to evaluate its potential as a human vaccine, prior to clinical trials. This information will provide the basis for industrial exploitation and future large scale production of various vaccines, particularly difficult ones such as those against parasites and HIV. The deliverables at the end of the project will be reports on procedures for the efficient and safe synthesis of products with potential as vaccines against a range of pathogens, ready for commercial exploitation.
One of the Partners is an industrial company and others will be invited to participate in a committee set up during the project with a view to planning the transition to commercial exploitation.
Champ scientifique (EuroSciVoc)
CORDIS classe les projets avec EuroSciVoc, une taxonomie multilingue des domaines scientifiques, grâce à un processus semi-automatique basé sur des techniques TLN. Voir: Le vocabulaire scientifique européen.
CORDIS classe les projets avec EuroSciVoc, une taxonomie multilingue des domaines scientifiques, grâce à un processus semi-automatique basé sur des techniques TLN. Voir: Le vocabulaire scientifique européen.
- sciences médicales et de la santé médecine fondamentale immunologie immunisation
- sciences naturelles sciences biologiques microbiologie virologie
- sciences naturelles sciences biologiques biochimie biomolécule
- sciences médicales et de la santé sciences de la santé maladie infectieuse virus à ARN VIH
- sciences médicales et de la santé médecine fondamentale pharmacologie et pharmacie produit pharmaceutique vaccins
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Coordinateur
LONDON
Royaume-Uni
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