Influenza and HIV viruses are characterized by high natural genetic variation in the genes encoding the major surface glycoproteins. This high genetic variation represents a major obstacle for the development of vaccines. The long-term goal of this project is to develop new molecular approaches for producing molecules capable of stimulating host immunity against influenza and HIV viruses. The first goal is to create (1) a chimeric Ig molecule bearing a nucleoprotein epitope recognized by T cells and (2) bifunctional antibody directed against hemagglutinin and T-cell receptors (TCR). These molecules will be used to enhance cell-mediated immunity against influenza virus, which helps to clear infected cells and slow the spread of viral infection. The second goal is to produce molecules able to enhance both humoral and cellular immunity against HIV. Studies on the enhancement of humoral immunity will be conducted by using antiidiotype antibodies carrying the internal image of the 503-535 epitope of the envelope gp120 protein. This epitope encompasses an immunodominant determinant (503-518) as well as a fusogenic determinant (526-535). To enhance the cell-mediated immunity we propose to create a chimeric molecule which will direct human CTL to HIV- infected cells. Such molecules can be used either as vaccines or as new immunotherapeutic agents.
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