Obiettivo
We propose to develop the replication defective influenza delNS1 virus as a vector for antigens derived from the SARS-associated corona virus (SARS-CoV) to a stage for use in clinical phase I trials. The resulting virus (Flu/SARS) will have the potential to induce immunity against both, influenza virus and SARS-CoV. First we will define relevant SARS-specific antigens. This will be achieved by the software suite, EpiScore and subsequent immunogenicity studies with peptides. The most promising antigens that evolve from this process will be introduced into the delNS1 virus vector. In parallel we will construct a delNS1 vector which can be used to effectively express foreign antigens. This will be achieved by expressing a model antigen in different sites of the delNS1 virus. The construct which shows the best balance between immunogenicity and level of attenuation will be used for expression of the defined SARS-antigens. The ability of the resulting construct (Flu/SARS) to induce neutralizing antisera, CTLs that destroy virus infected cells, to confer protection against viral challenge as well as their level of attenuation will be analysed in mice and in ferrets. The construct which shows the best profile according to these criteria will be produced, purified and filled under GMP-conditions. With the resulting vaccine lots, toxicology studies will be performed. The consortium of this proposal comprises the companies emergence which is renowned for its know how in defining epitopes, Green Hills Biotechnology which is highly experienced with in-vitro mutagenesis of influenza viruses, Bio test which has established mouse and ferret animal models for viral infections, Biaseparations which has developed a superior method for purification of live viruses, and the Goethe University of Frankfurt who was amongst the first who isolated the SARS-associated Coronavirus. Finally, Green Hills will cooperate with Bioreliance who is a leader in viral vaccine
Campo scientifico
Invito a presentare proposte
FP6-2003-LIFESCIHEALTH-I
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