Publication: Evidence that the erythrocyte invasion ligand PfRh2 is a target of protective immunity against Plasmodium falciparum malaria
Issued Date
2010-11-15
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ISSN
15506606
00221767
00221767
Other identifier(s)
2-s2.0-78650650970
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Immunology. Vol.185, No.10 (2010), 6157-6167
Suggested Citation
Linda Reiling, Jack S. Richards, Freya J.I. Fowkes, Alyssa E. Barry, Tony Triglia, Watcharee Chokejindachai, Pascal Michon, Livingstone Tavul, Peter M. Siba, Alan F. Cowman, Ivo Mueller, James G. Beeson Evidence that the erythrocyte invasion ligand PfRh2 is a target of protective immunity against Plasmodium falciparum malaria. Journal of Immunology. Vol.185, No.10 (2010), 6157-6167. doi:10.4049/jimmunol.1001555 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/29177
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Title
Evidence that the erythrocyte invasion ligand PfRh2 is a target of protective immunity against Plasmodium falciparum malaria
Abstract
Abs targeting blood-stage Ags of Plasmodium falciparum are important in acquired immunity to malaria, but major targets remain unclear. The P. falciparum reticulocyte-binding homologs (PfRh) are key ligands used by merozoites during invasion of erythrocytes. PfRh2a and PfRh2b are functionally important members of this family and may be targets of protective immunity, but their potential role in human immunity has not been examined. We expressed eight recombinant proteins covering the entire PfRh2 common region, as well as PfRh2a-and PfRh2b-specific regions. Abs were measured among a cohort of 206 Papua New Guinean children who were followed prospectively for 6 mo for reinfection and malaria. At baseline, Abs were associated with increasing age and active infection. High levels of IgG to all PfRh2 protein constructs were strongly associated with protection from symptomatic malaria and high-density parasitemia. The predominant IgG subclasses were IgG1 and IgG3, with little IgG2 and IgG4 detected. To further understand the significance of PfRh2 as an immune target, we analyzed PfRh2 sequences and found that polymorphisms are concentrated in an N-terminal region of the protein and seem to be under diversifying selection, suggesting immune pressure. Cluster analysis arranged the sequences into two main groups, suggesting that many of the haplotypes identified may be antigenically similar. These findings provide evidence suggesting that PfRh2 is an important target of protective immunity in humans and that Abs act by controlling blood-stage parasitemia and support its potential for vaccine development. Copyright © 2010 by The American Association of Immunologists, Inc.