INTRACELLULAR VIRUS NEUTRALIZATION BY IGA ANTIBODIES IN HOST DEFENSE IN VIVO

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Traditionally, mucosal IgA has been viewed as an immune barrier to prevent the adherence of viruses to epithelium. As such, resistance to viral infections best correlates with the presence of viral specific IgA antibodies in mucosal secretions. Recent studies employing an in vitro polarized epithelial monolayer system have suggested that polymeric IgA, as it is transported through the cell by the polymeric immunoglobulin receptor, can bind to intracellular viral proteins, effectively preventing viral replication. The focus of this proposal is to investigate intracellular neutralization of virus by polymeric IgA in vivo in murine models. Three specific aims are included. Initially, using monoclonal antibodies against the structural proteins of Sendai virus, we will examine the ability of IgA interrupt viral replication within murine tracheal epithelial cells in vivo. Secondly, since murine hepatocytes express the polymeric immunoglobulin receptor and transport polymeric IgA from the blood into the file, we will study the ability of IgA monoclonal antibodies directed against mouse hepatitis virus to interfere with viral replication in vivo within hepatocytes. Finally, we will investigate the effect of antigenic specificity on the ease with which and on the intracellular location where IgA neutralizes virus within both tracheal epithelial cells and hepatocytes in vivo in the murine models. Information generated by these studies should contribute to our understanding of the phenomenon of intracellular antibody neutralization of virus and to the development of safe, effective antiviral immunization procedures.