The studies proposed for the competitive renewal period will focus on three major areas of immune response to RSV in man and in experimental animal models. These include human studies on the role of immune response in the natural history and outcome of naturally acquired RSV infection. 1) It is planned to determined the nature and possible role of immune response to major glycoproteins of RSV (especially F and G) in various immunoglobulin isotypes in serum and secretions over the course of the RSV induced bronchiolitis and wheezing. Studies will be undertaken to examine the effect of treatment with ribavirin, an antiviral chemotherapeutic agent, on the development of IgE specific antibody response to RSV glycoproteins and on the outcome of RSV associated wheezing. The role of possible release of LTC4 and LTD4 in the pathogenesis of virus induced wheezing will also be studied. 2) Other studies are proposed to examine the mechanisms of immunopathology of RSV infection in experimentally induced pulmonary disease in BALB/c mice. If is hoped to define virus and host related determinants of lung disease in animals who had been previously immunized with parenterally administered RSV. These studies will also attempt to examine the influence of RSV infection on the uptake of other environmental antigens or dietary macromolecules available in the respiratory tract. 3) Finally, long term studies are planned to explore alternative approaches to the development of immunoprophylaxis against RSV. Studies will be carried out to determine the effectiveness of intestinal immunization with RSV or RSV glycoproteins in inducing RSV specific immunologic reactivity in the respiratory tract and in protection against respiratory reinfection challenge. It is also planned to determine if immunization with isolated glycoproteins rather than whole virus will selectively limit or prevent development or RSV specific IgE response during primary immunization and during subsequent reinfection challenge. These investigations will involve routine tissue culture, immunofluorescence, Elisa and conventional immunologic procedures currently used in our laboratory.
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