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

Lee, Nelson, Gatton, Michelle L., Pelecanos, Anita, Bubb, Martin, Gonzalez, Iveth, Bell, David, Cheng, Qin and McCarthy, James S. (2012) Identification of optimal epitopes for Plasmodium falciparum rapid diagnostic tests that target histidine-rich proteins 2 and 3. Journal of Clinical Microbiology, 50 4: 1397-1405.


Author Lee, Nelson
Gatton, Michelle L.
Pelecanos, Anita
Bubb, Martin
Gonzalez, Iveth
Bell, David
Cheng, Qin
McCarthy, James S.
Title Identification of optimal epitopes for Plasmodium falciparum rapid diagnostic tests that target histidine-rich proteins 2 and 3
Journal name Journal of Clinical Microbiology  (ERA 2012 Listed)    (ERA 2010 Rank A)   Check publisher's open access policy
Publication date 2012-04
Sub-type Article
DOI 10.1128/JCM.06533-11
Volume number 50
Issue number 4
ISSN 0095-1137;1098-660X
Start page 1397
End page 1405
Total pages 9
Place of publication Washington, United States
Publisher American Society for Microbiology
Collection year 2013
Language eng
Abstract 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.
Keyword Sequence Variation
Malaria Parasites
Performance
Culture
Pfhrp2
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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