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|Title:||Reticulocyte and erythrocyte binding-like proteins function cooperatively in invasion of human erythrocytes by malaria parasites|
|Citation:||Infection and Immunity, 2011; 79(3):1107-1117|
|Publisher:||American Society for Microbiology|
|Sash Lopaticki, Alexander G. Maier, Jennifer Thompson, Danny W. Wilson, Wai-Hong Tham, Tony Triglia, Alex Gout, Terence P. Speed, James G. Beeson, Julie Healer, and Alan F. Cowman|
|Abstract:||Plasmodium falciparum causes the most severe form of malaria in humans and invades erythrocytes using multiple ligand-receptor interactions. Two important protein families involved in erythrocyte binding are the erythrocyte binding-like (EBL) and the reticulocyte binding-like (RBL or P. falciparum Rh [PfRh]) proteins. We constructed P. falciparum lines lacking expression of EBL proteins by creating single and double knockouts of the corresponding genes for eba-175, eba-181, and eba-140 and show that the EBL and PfRh proteins function cooperatively, consistent with them playing a similar role in merozoite invasion. We provide evidence that PfRh and EBL proteins functionally interact, as loss of function of EBA-181 ablates the ability of PfRh2a/b protein antibodies to inhibit merozoite invasion. Additionally, loss of function of some ebl genes results in selection for increased transcription of the PfRh family. This provides a rational basis for considering PfRh and EBL proteins for use as a combination vaccine against P. falciparum. We immunized rabbits with combinations of PfRh and EBL proteins to test the ability of antibodies to block merozoite invasion in growth inhibition assays. A combination of EBA-175, PfRh2a/b, and PfRh4 recombinant proteins induced antibodies that potently blocked merozoite invasion. This validates the use of a combination of these ligands as a potential vaccine that would have broad activity against P. falciparum.|
|Keywords:||Erythrocytes; Reticulocytes; Animals; Rabbits; Humans; Plasmodium falciparum; Malaria; Protozoan Proteins; Malaria Vaccines; Antibodies, Protozoan; Immunoblotting; Enzyme-Linked Immunosorbent Assay; Coculture Techniques; Transfection; Reverse Transcriptase Polymerase Chain Reaction; Gene Knockout Techniques|
|Rights:||Copyright © 2011, American Society for Microbiology. All Rights Reserved.|
|Appears in Collections:||Microbiology and Immunology publications|
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