2nd generation Vaccibodies for infectious diseases

Aim: PI (Bjarne Bogen) and co-workers have recently reported on a novel vaccine technology, Vaccibodies, which appears very potent. The object of the present proposal is to further improve the design and immunogenicity of Vaccibodies (resulting in 2nd gen eration Vaccibodies). Background: New and better vaccines are still needed for many infectious diseases. We have recently described a novel type of recombinant vaccine molecule (Vaccibody) that can be delivered as a naked DNA vaccine. Transfected cells s ecrete Vaccibody protein that targets antigen presenting cells for efficient delivery of antigen and induction of strong immune responses in mice (Bogen and co-workers, Mol Ther 2006, J Immunol 2007, Vaccine 2007, Blood 2007 in press). Projects of the p roposal: We will establish improved 2nd generation Vaccibodies by (i) enhancing their targeting function, by (ii) increasing their polymerization, and by (iii) introducing a promiscuous T helper epitope. In addition, their mechanism of action will be defi ned by (iv) tracking fluorescent Vaccibodies in tissues and cells. Budget: Salary for a postdoc or PhD student for three years and consumables. Project plan and management: A postdoc or PhD student will construct the 2nd generation Vaccibodies describ ed above and test their immunogenicity in defined mouse models in PIs lab. Next, such 2nd generation Vaccibodies for influenza and HIV will be tested in animal models in the labs of Drs. H. von Boehmer and Dan Barouch, Harvard (postdok Inger Øynebråten, PhD student Gunnveig Grødland). A Norwegian company, Vaccibody, will handle IPR, and transfer of the technology to human application.