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Infection and Immunity, August 2004, p. 4376-4384, Vol. 72, No. 8
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.8.4376-4384.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Long-Term Multiepitopic Cytotoxic-T-Lymphocyte Responses Induced in Chimpanzees by Combinations of Plasmodium falciparum Liver-Stage Peptides and Lipopeptides

Lbachir BenMohamed,1,2,3 Alan Thomas,4 and Pierre Druilhe1*

Unité de Parasitologie Bio-Médicale, Institut Pasteur, 75015 Paris, France,1 Laboratory of Cellular and Molecular Immunology, Department of Ophthalmology, College of Medicine, University of California at Irvine, Irvine, California 92697-4375,2 Center for Immunology, University of California at Irvine, Irvine, California 92697-1450,3 Biomedical Primate Research Center, 2280 GH Rijswijk, The Netherlands4

Received 10 November 2003/ Returned for modification 16 January 2004/ Accepted 27 April 2004

Preclinical immunogenicity studies of 12 malaria peptides, selected from four Plasmodium falciparum antigens (Ags), namely, LSA1, LSA3, SALSA, and STARP, that are expressed at the pre-erythrocytic (sporozoite and liver) stages of the human parasite were carried out in chimpanzees. To strengthen their immunogenicity, six of these synthetic peptides were modified by the C-terminal addition of a single palmitoyl chain (lipopeptides) and delivered without adjuvant, whereas the remaining six unmodified peptides were emulsified and delivered by using Montanide ISA51 adjuvant. We have previously reported that these peptides and lipopeptides induce high B-cell and CD4+-T-helper responses in chimpanzees. In this report, we show their ability to induce multiepitopic and long-lasting antigen-specific CD8+ cytotoxic-T-lymphocyte (CTL) responses. The magnitude, consistency, and memory of CTL responses generated by LSA3 peptides point to the strong immunogenicity of this liver-stage Ag. These findings support the screening strategy used to select the four P. falciparum pre-erythrocytic Ags and emphasize their valuable immunogenic properties. The successful immunization of nonhuman primates with combinations of corresponding peptides in a mineral oil emulsion (ISA51) and lipopeptides in saline provide a vaccine formulation that can be tested in humans.

* Corresponding author. Mailing address: Institut Pasteur, 28 Rue du Dr Roux, 75015 Paris, France. Phone: 33 1 45 68 8578. Fax: 33 1 45 68 8640. E-mail: druilhe{at}pasteur.fr.

Editor: S. H. E. Kaufmann

Infection and Immunity, August 2004, p. 4376-4384, Vol. 72, No. 8
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.8.4376-4384.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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