2015
DOI: 10.1073/pnas.1415466112
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Multiprotein complex between the GPI-anchored CyRPA with PfRH5 and PfRipr is crucial for Plasmodium falciparum erythrocyte invasion

Abstract: Erythrocyte invasion by Plasmodium falciparum merozoites is a highly intricate process in which Plasmodium falciparum reticulocyte binding-like homologous protein 5 (PfRH5) is an indispensable parasite ligand that binds with its erythrocyte receptor, Basigin. PfRH5 is a leading blood-stage vaccine candidate because it exhibits limited polymorphisms and elicits potent strain-transcending parasite neutralizing antibodies. However, the mechanism by which it is anchored to the merozoite surface remains unknown bec… Show more

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Cited by 152 publications
(231 citation statements)
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“…Furthermore, even at such high antibody levels, growth inhibition is rarely absolute. Antibodies against cysteine‐rich protective antigen (CyRPA) (full length) in two‐cycle invasion assays showed 85% inhibition at 10 mg/ml,69 antibodies against Rh5 (full‐length) showed 83% inhibition in a one‐cycle invasion assay at 10 mg/ml 42,70 and a 40% invasion inhibition was observed for antibodies against Rh5 interacting protein (Ripr) (ectodomain) at 2 mg/ml in a one‐cycle assay 42. Similarly, antibodies against several other characterized antigens (such as MSPDBL‐1 and ‐2)71, 72 showed a comparable trend of invasion inhibition and require fairly large antibody concentrations.…”
Section: Antibodies and Protection: What We Have Learnt So Farmentioning
confidence: 99%
“…Furthermore, even at such high antibody levels, growth inhibition is rarely absolute. Antibodies against cysteine‐rich protective antigen (CyRPA) (full length) in two‐cycle invasion assays showed 85% inhibition at 10 mg/ml,69 antibodies against Rh5 (full‐length) showed 83% inhibition in a one‐cycle invasion assay at 10 mg/ml 42,70 and a 40% invasion inhibition was observed for antibodies against Rh5 interacting protein (Ripr) (ectodomain) at 2 mg/ml in a one‐cycle assay 42. Similarly, antibodies against several other characterized antigens (such as MSPDBL‐1 and ‐2)71, 72 showed a comparable trend of invasion inhibition and require fairly large antibody concentrations.…”
Section: Antibodies and Protection: What We Have Learnt So Farmentioning
confidence: 99%
“…This receptor-adhesin pair mediates an essential molecular event during parasite entry, and sequence polymorphisms within PfRh5 and/or basigin have been shown to modulate host tropism (16,17). The addition of antibodies against PfRh5, basigin, or PfRh5-interacting partners (PfRipr and PfCyRPA) in P. falciparum growth assays results in the strong inhibition of parasite growth across multiple strains (15,(18)(19)(20)(21). Further promising results show that Aotus nancymaae monkeys immunized with the anti-PfRh5 vaccine are protected against severe infection (22).…”
Section: Significancementioning
confidence: 99%
“…Nevertheless, substantial progress has been made in recent years, with the identification of a new generation of merozoite antigen targets that are essential and that exhibit relatively low levels of polymorphism, leading to induction of strain-transcending antibodies by vaccination in preclinical models (11). Three of these targets form a complex, including the P. falciparum reticulocyte-binding protein homolog 5 (RH5) (12), the cysteine-rich protective antigen (CyRPA) (13), and the RH5-interacting protein (Ripr) (14). Of these, vaccine development efforts are currently most advanced for RH5 (15).…”
Section: Introductionmentioning
confidence: 99%