Mucosal DNA vaccine immunization against measles with a highly attenuated Shigella flexneri vector

An intranasal vaccine vector would elicit protective inn;unity at the respi ratory mucosa, the portal of entry and the primary site for replication for measles virus (MV) and other respiratory viruses,In a murine model of pulm onary Shigella, we demonstrate here that a candidate-attenuated Shigella va ccine vector is safely tolerated in IFN-gamma deficient mice at an inoculum that is 1 million-fold higher than the inoculum of the wild-type parent st rain that would be lethal for greater than 90% of these mice. Also, followi ng intranasal inoculation, the Delta asd Shigella harboring a DNA MV vaccin e plasmid induces a vigorous MV-specific Th1-type (both CD8(+) CTL and IFN- gamma) and, to a lesser degree, Th2-type responses among splenocytes in add ition to low levels of IgG and IgA in the serum. Priming for MV-specific CT L responses was possible in mice that had prior infection with a wild-type Shigella of the same serotype, Remarkably, mice immunized by the intranasal route with attenuated Shigella harboring the DNA MV vaccine plasmid had a level of MV-specific CTL activity among splenocytes that was comparable wit h levels observed in mice immunized by the i,p. route with attenuated Salmo nella typhi harboring the same DNA vaccine plasmid, despite the fact that S higella remained localized to the lungs, yet Salmonella disseminated to the spleen following inoculation, Thus, Delta asd Shigella represents a very u seful vector for delivery of DNA vaccines to mucosal lymphoid tissues.