ELIMINATING A REGION OF RESPIRATORY SYNCYTIAL VIRUS ATTACHMENT PROTEIN ALLOWS INDUCTION OF PROTECTIVE IMMUNITY WITHOUT VACCINE-ENHANCED LUNG EOSINOPHILIA

In a murine model of respiratory syncytial virus disease, prior sensit ization to the attachment glycoprotein (G) leads to pulmonary eosinoph ilia and enhanced illness. Three different approaches were taken to di ssect the region of G responsible for enhanced disease and protection against challenge. First, mutant viruses, containing frameshifts that altered the COOH terminus of the G protein, were used to challenge mic e sensitized by scarification with recombinant vaccinia virus (rVV) ex pressing wild-type G. Second, cDNA expressing these mutated G proteins were expressed by rVV and used to vaccinate mice before challenge wit h wild-type respiratory syncytial virus (RSV). These studies identifie d residues 193-205 to be responsible for G-induced weight loss and lun g eosinophilia and showed that this region was not was not necessary f or induction of protective immunity. Third, mice were sensitized using an rVV that expressed only amino acids 124-203 of the G protein. Upon RSV challenge, mice sensitized with this rVV developed enhanced weigh t loss and eosinophilia. This is the first time that a region within R SV (amino acids 193-203) has been shown to be responsible for inductio n of lung eosinophilia and disease enhancement. Moreover, we now show that it is possible to induce protective immunity with an altered G pr otein without inducing a pathological response.