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Type I interferon as an adjuvant: immune mechanisms and preparation of new vaccines against the Epstein-Barr virus

Obiettivo



The Biotechnology programme includes the important task of developing vaccine research in Europe (area 5). Although effective vaccines for a number of infectious diseases are available, the immune mechanisms involved in the protection are not fully understood and additional efforts are needed for developing second generation vaccines against classical infectious diseases as well as new vaccines against yet unchallenged pathogens. A crucial issue in vaccine research is the identification of new adjuvant factors and mechanisms involved in the generation of a long-lasting protective immunity. Recent studies indicate that type I IFN (especially IFN-alpha) is an important factor for the activation and persistence of a protective CD8-T cell-mediated immune response against both infectious agents and tumours, thus suggesting that this cytokine can be considered a powerful vaccine adjuvant.
The general aims of our study are: i) to characterise the adjuvant effects of type I IFN in well defined mouse models; ii) to study the advantages of using IFN as an adjuvant in an animal model closely resembling the EBV infection in man (represented by immunocompetent mice infected with the MHV-68 virus); iii) to develop new vaccines against EBV to be tested in suitable human/mouse models in SCID mice. We will use different types of vaccine strategies, including direct DNA immunisation with the relevant genes as well as the use of recombinant viruses and transduced dendritic cells expressing viral peptides and IFN. These studies should lead to consider IFN-a as an effective adjuvant for some human vaccines. The choice of EBV as the initial human virus for this combined vaccine strategy relies on specific considerations (importance of CD8+ T cells in the control of EBV infection, existence of animal models for preclinical tests) and on the evaluation of the possible clinical impact of the new vaccines. In fact, an effective anti-EBV vaccine is expected to be clinically used for the control of certain EBV-induced diseases. All this could result in obvious social and economical benefits for the European Community.
The 5 groups joined in this proposal have complementary scientific backgrounds and technical skills. Partner 1 has a long-lasting experience on IFN, necessary for the accomplishment of all the parts of the project. Partner 2 has provided recent contributions of fundamental importance for considering type I IFN as an adjuvant; the work of this group will be mainly focused on the characterisation of the immunologic mechanisms underlying the adjuvant effects of IFN. Partner 3 is a world-wide expert in the MHV-68 mouse infection model; the participation of this group is strictly instrumental for the development of optimal vaccination strategies against EBV. Partner 4 has an extensive experience on the human immune response to viruses and, especially, on the pathogenesis of EBV infection and on the animal models necessary for testing the new anti-EBV vaccines. Partner 5 is an industry with a long-lasting interest on IFN and will assume the formal responsibility of determining the market interest on the new reagents, techniques and protocols.

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ISTITUTO SUPERIORE DI SANITA
Contributo UE
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Indirizzo
Viale Regina Elena 299
00161 ROMA
Italia

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