Service Communautaire d'Information sur la Recherche et le Développement - CORDIS


COMPUVAC Résumé de rapport

Project ID: 5246
Financé au titre de: FP6-LIFESCIHEALTH
Pays: France

Final Report Summary - COMPUVAC (Ration design and standardized evaluation of novel genetic vaccines.)

Recent progresses in virology and biotechnology has allowed the development of recombinant viral vectors and virus-like particles that are considered promising vehicles to deliver antigens in prophylactic and therapeutic vaccines against infectious diseases and cancer. While several potential vaccine designs exist, the lack of standardised tools to accurately assess, compare and select potential vaccine candidates prevents their cost-effective development.

On these grounds, COMPUVAC aimed to provide means for rational development of novel recombinant vaccines based on the use of gold standard antigens and standardised procedures for their qualitative and quantitative comparative evaluation of efficacy and safety / toxicity. To store, analyse and represent results on efficacy and safety / toxicity, as well as to predict good vector combinations, COMPUVAC also aimed at generating an interactive database and bioinformatics tools for data processing and 'intelligent' decision-making. Finally, COMPUVAC aimed at validating its concepts by applying the methodology for the development of a vaccine against HCV.

The achievement of the COMPUVAC project is best demonstrated / represented by the online publication of an interactive database that can now be used by the scientific community to comparatively assess future vaccines.

Vaccine vectors were engineered to express the T or B cell model antigens. After production and quality control, they were tested using standardised procedures to assess their immunogenicity in term of induction of T cell or B cell immune responses. In addition, gene expression profiles were produced in dendritic cell and regulatory T cell populations after vector injection. Results were then systematically quality checked, collected and stored into the Genetic vaccine decision support system (GEVADSS) database to produce a standardised report of each vector vaccine tested. In turn, multi-parameters analysis of the database were performed in order to evaluate the performance of vector platforms and to cross compare the different vector platforms. Following this strategy has successfully guided the design of an HCV vaccine candidate.

According to the original aims of the project, a good and operative level of standardisation has been reached. The intra-laboratory and inter-laboratory variations for the different assays were satisfactorily. Further reducing them would require significant additional efforts and resources that are not in balance with the potential gain. This standardisation effort was a key requisite to allow the cross comparison of vaccine vectors across laboratories, vaccine formulation. The portability of our methodology has been validated and demonstrates its availability and usefulness to the scientific community. The publication of SOPs on the COMPUVAC website constitutes an important contribution to the scientific community.

The construction and development of the GEVADSS was a very challenging aspect of the project, due to its interdisciplinary nature. The project partners, however, managed to bring together specialists from various disciplines and ensure good communication between them and understanding of each other's vocabulary.

This significant effort led to the successful implementation and release of a comprehensive and user-friendly software platform for vaccine vector development and evaluation. Moreover, the modular design of GEVADSS makes it suitable for further development and application to additional fields. The development of GEVADSS, which begun on day one of the project, will continue after its end (some features are still under validation and testing). GEVADSS will be open to the public and maintained with further development / improvement for at least a further two years and new test results will be added.

The database will be made available as a major online publication of COMPUVAC, and thus constitute a unique source of data for further vaccine vectors evaluation beyond the scope of the project. The GEVADSS database that contains the results of the evaluation of more than one hundred vectors expressing the same antigens is a unique asset for the scientific community. Its web-based accessibility should allow and prompt external scientist to continue study the results of the experiment stored, which could not be extensively done within the COMPUVAC timeframe. The COMPUVAC multi-parameters evaluation of vector vaccines allowed comparison of these vectors' behaviour. Such a comparison revealed no simple direct correlations between the different assays. This underlines the complexity of vector classification and emphasises that the database as a whole constitute a novel tool that should be analysed to make more subtle evaluation of vaccine vector properties. The work completed which is an introduction of systems immunology in the field of vaccination is pioneering the promising field of systems vaccinology, as recently stated by Pr. B. Pulendran: 'Despite their great success, we understand little about how effective vaccines stimulate protective immune responses. Two recent developments promise to yield such understanding: the appreciation of the crucial role of the innate immune system in sensing microorganisms and tuning immune responses, and advances in systems biology.'

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