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Infection and Immunity, June 2009, p. 2427-2435, Vol. 77, No. 6
0019-9567/09/$08.00+0     doi:10.1128/IAI.00048-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Antibodies to Reticulocyte Binding Protein-Like Homologue 4 Inhibit Invasion of Plasmodium falciparum into Human Erythrocytes{triangledown}

Wai-Hong Tham, Danny W. Wilson, Linda Reiling, Lin Chen, James G. Beeson, and Alan F. Cowman*

Walter and Eliza Hall Institute of Medical Research, Melbourne 3050, Australia

Received 14 January 2009/ Returned for modification 28 February 2009/ Accepted 17 March 2009

Plasmodium falciparum invasion into human erythrocytes relies on the interaction between multiple parasite ligands and their respective erythrocyte receptors. The sialic acid-independent invasion pathway is dependent on the expression of P. falciparum reticulocyte binding protein-like homologue 4 (PfRh4), as disruption of the gene abolishes the ability of parasites to switch to this pathway. We show that PfRh4 is present as an invasion ligand in culture supernatants as a 160-kDa proteolytic fragment. We confirm that PfRh4 binds to the surfaces of erythrocytes through recognition of an erythrocyte receptor that is neuraminidase resistant but trypsin and chymotrypsin sensitive. Serum antibodies from malaria-exposed individuals show reactivity against the binding domain of PfRh4. Purified immunoglobulin G raised in rabbits against the binding domain of PfRh4 blocked the binding of native PfRh4 to the surfaces of erythrocytes and inhibited erythrocyte invasion of parasites using sialic acid-independent invasion pathways and grown in neuraminidase-treated erythrocytes. Our results suggest PfRh4 is a potential vaccine candidate.

* Corresponding author. Mailing address: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia. Phone: 61393452555. Fax: 61393470852. E-mail: cowman{at}wehi.edu.au

{triangledown} Published ahead of print on 23 March 2009.

Editor: W. A. Petri, Jr.

Infection and Immunity, June 2009, p. 2427-2435, Vol. 77, No. 6
0019-9567/09/$08.00+0     doi:10.1128/IAI.00048-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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