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. 2006 Aug;44(8):2773-8.
doi: 10.1128/JCM.02557-05.

Effect of sequence variation in Plasmodium falciparum histidine- rich protein 2 on binding of specific monoclonal antibodies: Implications for rapid diagnostic tests for malaria

Nelson Lee  1 , Joanne Baker, Kathy T Andrews, Michelle L Gatton, David Bell, Qin Cheng, James McCarthy
Affiliations

Effect of sequence variation in Plasmodium falciparum histidine- rich protein 2 on binding of specific monoclonal antibodies: Implications for rapid diagnostic tests for malaria

Nelson Lee et al. J Clin Microbiol. 2006 Aug.

Abstract

The ability to accurately diagnose malaria infections, particularly in settings where laboratory facilities are not well developed, is of key importance in the control of this disease. Rapid diagnostic tests (RDTs) offer great potential to address this need. Reports of significant variation in the field performance of RDTs based on the detection of Plasmodium falciparum histidine-rich protein 2 (HRP2) (PfHRP2) and of significant sequence polymorphism in PfHRP2 led us to evaluate the binding of four HRP2-specific monoclonal antibodies (MABs) to parasite proteins from geographically distinct P. falciparum isolates, define the epitopes recognized by these MABs, and relate the copy number of the epitopes to MAB reactivity. We observed a significant difference in the reactivity of the same MAB to different isolates and between different MABs tested with single isolates. When the target epitopes of three of the MABs were determined and mapped onto the peptide sequences of the field isolates, significant variability in the frequency of these epitopes was observed. These findings support the role of sequence variation as an explanation for variations in the performance of HRP2-based RDTs and point toward possible approaches to improve their diagnostic sensitivities.

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Figures

FIG. 1.
FIG. 1.
Dot blot analysis of protein extracts from eight P. falciparum isolates. Parasite protein extracts were prepared in doubling dilutions of 1/2 to 1/2,048 before application to each membrane as indicated at the bottom of each panel. Membranes were then incubated with the four monoclonal antibodies 4A5, 3A4, 2G12-1C12, and 1E1-A9.
FIG. 2.
FIG. 2.
Control dot blot analysis of protein extracts from uninfected red blood cells (RBC) and two P. falciparum isolates. Protein extracts were prepared at a dilution of 1/8 before application onto each membrane, as indicated at the bottom of each row. Membranes were then incubated at a dilution of 1/2,000 with the four monoclonal antibodies 4A5, 3A4, 2G12-1C12, and 1E1-A9.
FIG. 3.
FIG. 3.
Western blot analysis of protein extracts of two P. falciparum isolates, TM91-C32B and PH4, using the four monoclonal antibodies 4A5, 3A4, 2G12-1C12, and 1E1-A9. Molecular masses (in kilodaltons) are shown at the left side of each panel.
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