The SAS proposals for participation in FP6 projects
are listed in blocks according to the FP6 priority theme structure

FP6 priority
1.1.1   Genomics and Biotechnology for Health
Title of the proposal

Polyvalent vaccine incorporating Murine herpesvirus antigens as a tool for study of immune host response to human gammaherpesvirus infection

Slovak Academy of Sciences, Institute of Virology
Dubravska cesta 9, 842 45 Bratislava, Slovak Republic
+421 2 59302437

Research subject for a potential FP6 project

Human gammaherpesvirus EBV and HHV8 cause life long latent infection of host B cell compartment which is associated with a number of malignancies (Burkittīs lymphoma, nasopha-ryngeal carcinoma and Kaposiīs sarcoma). Both they are lacking of animal model systems to study their pathogenesis. Related to them Murine gamma herpesvirus /MHV/ offers an animal model for study of basis of host-immune response and for development of vaccine strategy. Only a few strategies against MHV infection have been tried till now. Immunization with MHV 68 late gene product gp150 (homologue of EBV gp340) resulted in production of MHV neutralizing antibodies but did not prevent the establishment of virus latency. On the other hand using latency-associated MHV 68 M2 antigen decreased a latent viral load but had no effect on the acute lung infection. The aim of project is to try to make effective polyvalent vaccine against MHV which both could to limit virus replication and to reduce/eliminate the latent infection. Results generated from using an appropriate combination of lytic (e.g. M3, gp150) and latency-associated (e.g. K3, M2, M11, viral tRNA) antigens for pre-exposure and/or post exposure vaccination could enhance our knowledge about mainly those antigens which have a broad effect on antigen-specific as well as non-specific elements of host immune response. Our research team is dealing with characterization of MHV 72/MHV 68 latency- associated genes expressed in different organs of immunocompetent mice depending on the route of infection as well as with characterization of MHV72. Our recent data show that some of its latency-associated genes are different from MHV68. Thus, MHV 72 could serves as a source of wider palette of antigens combination to be tried in suggested polyvalent vaccine. A contribution of our research group will lie on preparation of vaccine MHV 72/MHV 68 antigens candidates, vaccination of mice and following evaluation of host response to vaccination (viral replication, latent infection of mouse organs, reactivation from latency) studying of elements which are required to control of infection and which are involved in immune subversion strategies of gammaherpesviruses

Recent international cooperation of the research team

Possible partner: Division of Virology, University of Cambridge, UK

Proposerīs relevant publications related to the research subject

Immunophenotypic study of atypical lymphocytes generated in peripheral blood and spleen of nude mice after MHV-72 infection. Raslova, H., Mistrikova, J., Kudelova, M., Mishal, Z., Sarasin, A., Blangy,D., Berebbi,M. Viral Immunol. 13, 313-327 /2000/The bystander effect mediated by the new murine gammaherpesvirus 72-thymidine kinase/5°-fluoro-2°-deoxyuridine (MHV72-TK/5-FUdR) system in vitro. Raslova, H., Matis, J., Rezuchova I., Macakova, K., Berebbi, M., Kudelova M. Antiviral Chemistry & Chemotherapy 11, 273-282 /2000/Susceptibility of mouse mammary glands to murine gammaherpesvirus 72 (MHV-72) infection: evidence of MHV-72 transmission via breast milk. Raslova, H., Berebbi, M., Rajcani, J., Sarasin, A., Matis, J., Kudelova M. Microbial Pathogenesis 31, 47-58 /2001/