Lopaticki, S.Maier, A.Thompson, J.Wilson, D.Tham, W.Triglia, T.Gout, A.Speed, T.Beeson, J.Healer, J.Cowman, A.Adams, J.H.2015-01-122015-01-122011Infection and Immunity, 2011; 79(3):1107-11170019-95671098-5522http://hdl.handle.net/2440/88610Plasmodium 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.enCopyright © 2011, American Society for Microbiology. All Rights Reserved.ErythrocytesReticulocytesAnimalsRabbitsHumansPlasmodium falciparumMalariaProtozoan ProteinsMalaria VaccinesAntibodies, ProtozoanImmunoblottingEnzyme-Linked Immunosorbent AssayCoculture TechniquesTransfectionReverse Transcriptase Polymerase Chain ReactionGene Knockout TechniquesJournal article002013804010.1128/IAI.01021-100002877002000132-s2.0-7995229931614538Wilson, D. [0000-0002-5073-1405]