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Infection and Immunity, July 2002, p. 3479-3492, Vol. 70, No. 7
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.7.3479-3492.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Plasmodium vivax Promiscuous T-Helper Epitopes Defined and Evaluated as Linear Peptide Chimera Immunogens

Ivette Caro-Aguilar,^1, Alexandra Rodríguez,^1, J. Mauricio Calvo-Calle,² Fanny Guzmán,¹ Patricia De la Vega,³ Manuel Elkin Patarroyo,¹ Mary R. Galinski,⁴ and Alberto Moreno^4*

Fundación Instituto de Inmunología de Colombia (FIDIC), Santafé de Bogotá, Colombia,¹ Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, New York,² Naval Medical Research Center, Silver Spring, and Department of Microbiology, School of Medicine, University of Maryland, Baltimore, Maryland,³ Emory Vaccine Research Center at Yerkes Regional Primate Research Center of Emory University, Atlanta, Georgia⁴

Received 20 November 2001/ Returned for modification 18 January 2002/ Accepted 25 March 2002

Clinical trials of malaria vaccines have confirmed that parasite-derived T-cell epitopes are required to elicit consistent and long-lasting immune responses. We report here the identification and functional characterization of six T-cell epitopes that are present in the merozoite surface protein-1 of Plasmodium vivax (PvMSP-1) and bind promiscuously to four different HLA-DRB1_* alleles. Each of these peptides induced lymphoproliferative responses in cells from individuals with previous P. vivax infections. Furthermore, linear-peptide chimeras containing the promiscuous PvMSP-1 T-cell epitopes, synthesized in tandem with the Plasmodium falciparum immunodominant circumsporozoite protein (CSP) B-cell epitope, induced high specific antibody titers, cytokine production, long-lasting immune responses, and immunoglobulin G isotype class switching in BALB/c mice. A linear-peptide chimera containing an allele-restricted P. falciparum T-cell epitope with the CSP B-cell epitope was not effective. Two out of the six promiscuous T-cell epitopes exhibiting the highest anti-peptide response also contain B-cell epitopes. Antisera generated against these B-cell epitopes recognize P. vivax merozoites in immunofluorescence assays. Importantly, the anti-peptide antibodies generated to the CSP B-cell epitope inhibited the invasion of P. falciparum sporozoites into human hepatocytes. These data and the simplicity of design of the chimeric constructs highlight the potential of multimeric, multistage, and multispecies linear-peptide chimeras containing parasite promiscuous T-cell epitopes for malaria vaccine development.

Editor: S. H. E. Kaufmann

Present address: Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, N.Y.

Present address: Departamento de Biologia Molecular, Instituto de Investigaciones Biomedicas, UNAM, Mexico, D.F. Mexico.

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