Based on the knowledge that the mucosal immune system and its predominant effector, secretory IgA, forms the first line of defense at the interface between the pulmonary epithelial surface an the external environment and that resistance to respiratory viral infections correlates with the presence of viral specific IgA antibodies in the mucosal secretions, this proposal seeks to determine the mechanism(s) by which secretory IgA neutralizes virus at the mucosal surface. This project will employ a model system of a natural respiratory pathogen of mice, Sendai virus, a member of the parainfluenza group. A series of anti-Sendai IgA monoclonal antibodies has been generated, and characterized for antigenic specificity and in vitro biologic activities. These anti- viral IgA monoclonal antibodies will be used in three major kinds of studies. First, passive immunization studies have been designed to determine and compare the protection afforded by locally versus systemically administered antibody of IgA and other isotypes against subsequent viral challenge. Second, radiolabeled monoclonal antibodies will be used to examine the transport kinetics of serum dimeric and monomeric IgA as compared to IgG into the pulmonary mucosal secretions. Third, the ability of IgA antibody to neutralize virus within mucosal epithelial cells in a polarized tissue culture system will be assessed. Information generated from these experiments should aide in the development of more effective strategies for immunization against common human respiratory viral pathogens.
