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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Identification of optimal epitopes for Plasmodium falciparum rapid diagnostic tests that target histidine-rich proteins 2 and 3
Journal of Clinical Microbiology, Volume 50, No. 4, Year 2012
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Description
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. Copyright © 2012, American Society for Microbiology. All Rights Reserved.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3318543/bin/supp_50_4_1397__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC3318543/bin/supp_50.4.1397_JCM-JCM06533-11-s01.pdf
Authors & Co-Authors
Lee, Nelson
Australia, Brisbane
The University of Queensland
Australia, Sydney
The University of Sydney
Gatton, Michelle L.
Australia, Brisbane
Qimr Berghofer Medical Research Institute
Pelecanos, Anita
Australia, Brisbane
Qimr Berghofer Medical Research Institute
Bubb, Martin
South Africa, Pinetown
National Bioproducts Institute
González, Iveth J.
Switzerland, Geneva
Foundation for Innovative new Diagnostics, Switzerland
Bell, David R.
Switzerland, Geneva
Foundation for Innovative new Diagnostics, Switzerland
Cheng, Qin
Australia, Brisbane
Qimr Berghofer Medical Research Institute
Australia, Enoggera
Australian Army Malaria Institute
McCarthy, James S.
Australia, Brisbane
The University of Queensland
Statistics
Citations: 61
Authors: 8
Affiliations: 6
Identifiers
Doi:
10.1128/JCM.06533-11
ISSN:
00951137
e-ISSN:
1098660X
Research Areas
Genetics And Genomics
Health System And Policy
Infectious Diseases