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Infection and Immunity, April 2006, p. 2277-2285, Vol. 74, No. 4
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.4.2277-2285.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Immunization with a Circumsporozoite Epitope Fused to Bordetella pertussis Adenylate Cyclase in Conjunction with Cytotoxic T-Lymphocyte-Associated Antigen 4 Blockade Confers Protection against Plasmodium berghei Liver-Stage Malaria

Susanne Tartz,1 Jana Kamanova,4 Marcela Simsova,4 Peter Sebo,4 Stefanie Bolte,2 Volker Heussler,2 Bernhard Fleischer,1,3 and Thomas Jacobs1*

Department of Immunology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany,1 Department of Parasitology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany,2 Institute of Immunology, University Hospital, Hamburg, Germany,3 Laboratory of Molecular Biology of Bacterial Pathogens, Cell and Molecular Microbiology Division, Czech Academy of Sciences, Institute of Microbiology, Prague, Czech Republic4

Received 22 November 2005/ Returned for modification 22 December 2005/ Accepted 14 January 2006

The adenylate cyclase toxoid (ACT) of Bordetella pertussis is capable of delivering its N-terminal catalytic domain into the cytosol of CD11b-expressing professional antigen-presenting cells such as myeloid dendritic cells. This allows delivery of CD8+ T-cell epitopes to the major histocompatibility complex (MHC) class I presentation pathway. Recombinant detoxified ACT containing an epitope of the Plasmodium berghei circumsporozoite protein (CSP), indeed, induced a specific CD8+ T-cell response in immunized mice after a single application, as detected by MHC multimer staining and gamma interferon (IFN-{gamma}) ELISPOT assay. This CSP-specific response could be significantly enhanced by prime-boost immunization with recombinant ACT in combination with anti-CTLA-4 during the boost immunization. This increased response was accompanied by complete protection in a number of mice after a challenge with P. berghei sporozoites. Transient blockade of CTLA-4 may overcome negative regulation and hence provide a strategy to enhance the efficacy of a vaccine by amplifying the number of responding T cells.

* Corresponding author. Mailing address: Department of Immunology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany. Phone: 49 (0) 40-42818-243. Fax: 49 (0) 40-42818-400. E-mail: tjacobs{at}bni.uni-hamburg.de.

Editor: W. A. Petri, Jr.

Infection and Immunity, April 2006, p. 2277-2285, Vol. 74, No. 4
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.4.2277-2285.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kamanova, J., Kofronova, O., Masin, J., Genth, H., Vojtova, J., Linhartova, I., Benada, O., Just, I., Sebo, P. (2008). Adenylate Cyclase Toxin Subverts Phagocyte Function by RhoA Inhibition and Unproductive Ruffling. J. Immunol. 181: 5587-5597 [Abstract] [Full Text]  


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