Targeting improves the efficacy of a DNA vaccine against Corynebacterium pseudotuberculosis in sheep

A large-scale DNA vaccination trial was performed with sheep to investigate whether an antigen targeted by CTLA-4 enhanced and accelerated the humoral immune response. Vaccination with genetically detoxified phospholipase D ( Delta PLD) has been shown to be effective, at least partially; against Cory nebacterium pseudotuberculosis, the causal agent of caseous lymphadenitis i n sheep. CTLA-4 binds to B7 on antigen-presenting cells and thus was used t o direct the fusion antigens to sites of immune induction. Here we demonstr ated that targeting Delta PLD as a CTLA-4 fusion protein significantly enha nced the speed, magnitude, and longevity of the antibody response compared to that obtained with DNA encoding Delta PLD. While all groups of sheep vac cinated with DNA encoding Delta PLD were afforded better protection against an experimental challenge with C. pseudotuberculosis than those immunized with an irrelevant plasmid or those left unimmunized. the best protection n as provided by the targeted DNA vaccine. me propose that targeting antigens to antigen-presenting cells offers a generic strategy for enhancing the ef ficacy of DNA vaccines.