Selection of Glutamate-Rich Protein Long Synthetic Peptides for Vaccine Development: Antigenicity and Relationship with Clinical Protection and Immunogenicity

doi:10.1128/IAI.69.9.5223-5229.2001

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Infection and Immunity, September 2001, p. 5223-5229, Vol. 69, No. 9
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.9.5223-5229.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Selection of Glutamate-Rich Protein Long Synthetic Peptides for Vaccine Development: Antigenicity and Relationship with Clinical Protection and Immunogenicity

Michael Theisen,¹^,^* Daniel Dodoo,² Aissatou Toure-Balde,³ Soe Soe,⁴^,⁵ Giampietro Corradin,⁶ Kwadwo K. Koram,² Jørgen A. L. Kurtzhals,²^,⁷^,⁸ Lars Hviid,⁷^,⁸ Thor Theander,⁷^,⁸ Bartholomew Akanmori,² Mohamadou Ndiaye,³ and Pierre Druilhe⁴

Department of Clinical Biochemistry, Statens Serum Institut,¹ Centre for Medical Parasitology at Department of Infectious Diseases, Copenhagen University Hospital,⁷ and Institute for Medical Microbiology and Immunology, University of Copenhagen,⁸ Copenhagen, Denmark; Immunology, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana²; Institut Pasteur, Dakar, Senegal³; Laboratoire de Parasitologie Médicale, Institut Pasteur, Paris, France⁴; Department of Medical Research, Yangon, Myanmar⁵; and Institute of Biochemistry, Lausanne, Switzerland⁶

Received 8 January 2001/Returned for modification 15 March 2001/Accepted 24 May 2001

Antibodies against three long synthetic peptides (LSPs) derived from the glutamate-rich protein (GLURP) of Plasmodium falciparumwere analyzed in three cohorts from Liberia, Ghana, and Senegal.Two overlapping LSPs, LR67 and LR68, are derived from the relativelyconserved N-terminal nonrepeat region (R0), and the third, LR70,is derived from the R2 repeat region. A high prevalence of antibodyresponses to each LSP was observed in all three areas of endemicinfection. Levels of cytophilic immunoglobulin G (IgG) antibodiesagainst both GLURP regions were significantly correlated withprotection from clinical P. falciparum malaria. Protected childrenfrom the Ghana cohort possessed predominantly IgG1 antibodiesagainst the nonrepeat epitope and IgG3 antibodies against therepeat epitope. T-cell proliferation responses, studied in thecohort from Senegal, revealed that T-helper-cell epitopes wereconfined to the nonrepeat region. When used as immunogens, theLR67 and LR68 peptides elicited strong IgG responses in outbredmice and LR67 also induced antibodies in mice of different H-2haplotypes, confirming the presence of T-helper-cell epitopesin these constructs. Mouse antipeptide antisera recognized parasiteproteins as determined by immunofluorescence and immunoblotting.This indicates that synthetic peptides derived from relativelyconserved epitopes of GLURP might serve as useful immunogens forvaccination against P. falciparummalaria.

^* Corresponding author. Mailing address: Department of Clinical Biochemistry, Statens Serum Institut, Artillerivej 5, DK-2300Copenhagen S, Denmark. Phone: (45) 32683779. Fax: (45) 32683228.E-mail: mth{at}ssi.dk.

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