Reticulocyte and Erythrocyte Binding-Like Proteins Function Cooperatively in Invasion of Human Erythrocytes by Malaria Parasites

Lopaticki, S; Maier, AG; Thompson, J; Wilson, DW; Tham, WH; Triglia, T; Gout, A; Speed, TP; Beeson, JG; Healer, J; Cowman, AF

Author(s): Lopaticki, S; Maier, AG; Thompson, J; Wilson, DW; Tham, WH; Triglia, T; Gout, A; Speed, TP; Beeson, JG; Healer, J; Cowman, AF;
Details: Publication Year 2011-03,Volume 79,Issue #3,Page 1107-1117
Journal Title: INFECTION AND IMMUNITY
Publication Type: Journal Article
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.
Publisher: AMER SOC MICROBIOLOGY
Keywords: PLASMODIUM-FALCIPARUM INVASION; INHIBITORY ANTIBODIES; RECEPTOR SPECIFICITY; ADHESIVE PROTEINS; GLYCOPHORIN-C; LIGAND; HOMOLOG; ANTIGEN; PATHWAYS; VIVAX
Publisher's Version: https://doi.org/10.1128/IAI.01021-10
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2011-03-01 12:00:00