The objectives of this proposal are: 1. To further delineate the antigenic sites of the influenza A neuraminidase by characterizing sequence changes in variants occurring naturally or selected under pressure of monoclonal antibodies. 2. To delineate the nature of the antigen - antibody complementary surfaces by sequence analysis of the antigen - binding (Fab) fragment derived from an anti-neuraminidase monoclonal Antibody. This sequence analysis is required for interpretation of the X-ray diffraction analyses being done by Dr. P. Colman of neuraminidase, variant neuraminidases, and the Fab fragment. 3. To generate, by recombinant DNA methods, specific mutants of the influenza virus surface antigens and to test the mutant polypeptides for changes in biological activity. Since almost all the variants selected with monoclonal antibodies cannot be distinguished with polyclonal antisera, it is unlikely that these would have any survival advantage in an immune population. We therefore aim to create specific mutants, based on the sequence changes known to occur in epidemiologically significant field strains, which show considerable differences from the antigens of parental virus when tested with polyclonal antisera. We hope that the detailed knowledge gained on the molecular mechanism of antigenic variation in the hemagglutinin and neuraminidase will lead to the development of ways to control influenza infection in man.
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