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Infection and Immunity, December 1999, p. 6434-6438, Vol. 67, No. 12
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Targeting Improves the Efficacy of a DNA Vaccine against Corynebacterium pseudotuberculosis in Sheep

Paul J. Chaplin,1,* Robert De Rose,1 Jefferey S. Boyle,2 Peter McWaters,1 Julie Kelly,1 Jan M. Tennent,1 Andrew M. Lew,2 and Jean-Pierre Y. Scheerlinck1

Cooperative Research Centre for Vaccine Technology Unit, CSIRO Animal Health,1 and The Walter and Elisa Hall Institute for Medical Research, Royal Melbourne Hospital,2 Parkville, Victoria 3052, Australia

Received 1 March 1999/Returned for modification 7 June 1999/Accepted 14 September 1999

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 Corynebacterium pseudotuberculosis, the causal agent of caseous lymphadenitis in sheep. CTLA-4 binds to B7 on antigen-presenting cells and thus was used to direct the fusion antigens to sites of immune induction. Here we demonstrated that targeting Delta PLD as a CTLA-4 fusion protein significantly enhanced the speed, magnitude, and longevity of the antibody response compared to that obtained with DNA encoding Delta PLD. While all groups of sheep vaccinated 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 was provided by the targeted DNA vaccine. We propose that targeting antigens to antigen-presenting cells offers a generic strategy for enhancing the efficacy of DNA vaccines.

* Corresponding author. Present address: Bavarian Nordic Research Institute GmbH, Fraunhoferstrasse 18b, D-82152 Martinsried, Germany. Phone: 49-89-85651315. Fax: 49-89-85651333. E-mail: chaplin{at}bavarian-nordic.de.

Infection and Immunity, December 1999, p. 6434-6438, Vol. 67, No. 12
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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