Identification of optimal epitopes for Plasmodium falciparum rapid diagnostic tests that target histidine-rich proteins 2 and 3

Autor: Iveth J. González, Michelle L. Gatton, Nelson Lee, James S. McCarthy, Qin Cheng, Martin Bubb, Anita Pelecanos, David Bell
Rok vydání: 2012
Předmět:
Microbiology (medical)
medicine.drug_class
Plasmodium falciparum/*immunology
Plasmodium falciparum
Amino Acid Motifs
Molecular Sequence Data
Protozoan Proteins
Antigens
Protozoan
Receptors
Fc
Computational biology
Monoclonal antibody
Sensitivity and Specificity
Epitope
Antibodies
Epitopes
PMC3318543
Protozoan Proteins/chemistry/*immunology
parasitic diseases
Receptors
medicine
Humans
Amino Acid Sequence
Malaria
Falciparum
Antigens
Peptide sequence
Gene
060502 Infectious Agents
Reagent Strips
biology
Protein Stability
Antibodies
Monoclonal
Monoclonal/chemistry
medicine.disease
biology.organism_classification
Virology
110800 MEDICAL MICROBIOLOGY
Protozoan/chemistry/*immunology
Malaria
Epitope mapping
Epitopes/chemistry/*immunology
Parasitology
Identification (biology)
Epitope Mapping
Falciparum/*diagnosis/immunology
Zdroj: Journal of Clinical Microbiology
ISSN: 2381-3652
Popis: Rapid diagnostic tests (RDTs) represent important tools to diagnose malaria infection. To improve understanding of the variable performance of RDTs that detect the major target in Plasmodium falciparum , namely, histidine-rich protein 2 (HRP2), and to inform the design of better tests, we undertook detailed mapping of the epitopes recognized by eight HRP-specific monoclonal antibodies (MAbs). To investigate the geographic skewing of this polymorphic protein, we analyzed the distribution of these epitopes in parasites from geographically diverse areas. To identify an ideal amino acid motif for a MAb to target in HRP2 and in the related protein HRP3, we used a purpose-designed script to perform bioinformatic analysis of 448 distinct gene sequences from pfhrp2 and from 99 sequences from the closely related gene pfhrp3 . The frequency and distribution of these motifs were also compared to the MAb epitopes. Heat stability testing of MAbs immobilized on nitrocellulose membranes was also performed. Results of these experiments enabled the identification of MAbs with the most desirable characteristics for inclusion in RDTs, including copy number and coverage of target epitopes, geographic skewing, heat stability, and match with the most abundant amino acid motifs identified. This study therefore informs the selection of MAbs to include in malaria RDTs as well as in the generation of improved MAbs that should improve the performance of HRP-detecting malaria RDTs.
Databáze: OpenAIRE
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