A Single Intramuscular Injection with an Adenovirus- Expressing IL-12 Protects BALB/c Mice Against Leishmania major Infection, While Treatment with an IL-4-Expressing Vector Increases Disease Susceptibility in B10.D2 Mice

作者: Jack Gauldie , Claudia Raja Gabaglia , Eli E. Sercarz , Frank L. Graham , Brian Pedersen

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摘要: Experimental infection of the susceptible BALB/c (H-2d) mouse with intracellular parasite Leishmania major induces a predominant Th2-type T cell response that eventually leads to death. In contrast, resistant B10.D2 strain develops Th1 cells control replication and disease. this study, we tested ability recombinant adenovirus vector-expressing IL-12 skew immune in direction prevent leishmaniasis mice. We report mice treated Ad5IL-12 vector on same day as parasitic challenge are significantly protected against acquired long-lasting immunity, because upon rechallenge L. parasites they were The vector-derived expression was transient highly localized tissue after i.m. injection; it caused an increase number Ag-specific IFN-gamma-secreting lymphocytes enhanced NK activity draining popliteal node. given injections adenovirus-expressing IL-4 displayed greater susceptibility disease, severe lesions produced some infected animals. These results suggest potential use adenoviruses expressing cytokines potent immunomodulatory agents for generation protective responses pathogens.

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