MOLECULAR ANALYSIS OF POLIOVIRUS NEUTRALIZING EPITOPES

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The aim of the proposed research is to contribute to a more detailed molecular description of the host antibody response to poliovirus virions. It is proposed that a combination of molecular biologic and immunologic approaches be used to determine A) the immunogenic sites on the poliovirus type 1 virion, specifically the neutralization determinants, B) the viral antigenic determinants recognized by the antivirion antibody response of susceptible and nonsusceptible hosts. To achieve these goals, monoclonal antibodies of predetermined linear antigenic specificity and monoclonal antibodies recognizing virion determinants will be used in conjunction with a recombinant DNA expression library expressing the different epitopes of the virus: 1) To identify the antigenic determinants present on the virion surface to which neutralizing antibodies bind, resulting in loss of infectivity; to isolate mutations in the antigenic determinants which result in loss of epitope recognition by the antibodies and in generation of neutralization resistant viruses and 2) To characterize the spectrum of poliovirus epitopes recognized by antibodies found in the sera from poliovirus-immunized mice and rats and from poliomyelitis patients. The host immune response to the virion is particularly important for a thorough understanding of poliovirus disease pathogenesis. The health relatedness of this proposal derives from its contribution to the understanding of molecular mechanism of viral pathogenesis and to the basis of host protection by poliovirus vaccines.