Affinage · Plasmodium

RIPR

PF3D7_0323400 · Rh5 interacting protein

Annotated
2026-09-07
86 papers in source corpus 14 papers cited in narrative 14 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RIPR (PF3D7_0323400) is a large, cysteine-rich EGF-domain-containing merozoite protein that is essential for Plasmodium falciparum erythrocyte invasion, functioning as a core member of the PfRh5-based invasion complex (PMID:21909261, PMID:27374406). First identified as a ~123 kDa protein with 10 EGF-like domains and 87 cysteines, it is processed in mature schizonts into two associating polypeptides, localizes to apical micronemes, and is released during invasion to form a complex with the rhoptry protein PfRh5 (PMID:21909261). Because RIPR lacks a transmembrane domain or GPI anchor, its incorporation into a heterotrimeric complex with PfRh5 and the GPI-anchored CyRPA (the RCR complex) provides both its membrane association and its erythrocyte-engaging function (PMID:25583518, PMID:30542156). Cryo-EM shows that CyRPA (via blades 4–6 of its β-propeller) bridges PfRh5 and RIPR, that the assembled complex binds and inserts into host erythrocyte membranes more effectively than PfRh5 alone, and that RIPR consists of a structured multidomain core flexibly linked to an elongated C-terminal tail (PMID:30542156, PMID:38123677). This tail anchors the complex to the merozoite membrane by binding the PfPTRAMP–PfCSS heterodimer, extending the assembly into the pentameric PCRCR complex that stabilizes merozoite–erythrocyte membrane contact upstream of tight-junction formation and Ca2+ release in the host cell (PMID:27374406, PMID:36396942, PMID:38123677). Conditional loss of RIPR blocks invasion, establishing its essentiality (PMID:27374406). Growth-inhibitory antibody epitopes cluster in RIPR's C-terminal EGF-like domains, which mediate the PfRh5 and SEMA7A interactions and represent a synergistic vaccine target (PMID:30965383, PMID:32313230, PMID:38849365, PMID:42285102). Outside the Laverania subgenus, RIPR retains an essential invasion role but its complex context diverges: in P. knowlesi the ortholog is essential yet forms a distinct trimeric complex without CyRPA or an RH5-like partner (PMID:31185066), while the PTRAMP–CSS–RIPR (PCR) core is conserved across P. falciparum, P. vivax, and P. knowlesi (PMID:41587959).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2011 High

    Establishing that a novel cysteine-rich protein physically partners with the invasion ligand PfRh5 defined RIPR as a functional component of the invasion machinery rather than an incidental merozoite protein.

    Evidence Co-IP/mass spectrometry, immunofluorescence, and antibody-based invasion inhibition in P. falciparum

    PMID:21909261

    Open questions at the time
    • Molecular function of the processed RIPR polypeptides not defined
    • Erythrocyte receptor engagement not identified
    • Mechanism of surface anchoring unknown given absence of transmembrane/GPI motifs
  2. 2015 High

    Identifying CyRPA as a GPI-anchored third partner resolved how the anchorless RIPR/PfRh5 pair is tethered to the merozoite surface, defining the heterotrimeric RCR complex.

    Evidence Native complex co-immunoprecipitation, GPI-linkage biochemical assay, and immunofluorescence in P. falciparum

    PMID:25583518

    Open questions at the time
    • Stoichiometry and assembly order not resolved
    • Functional consequence of complex assembly on invasion not directly tested
  3. 2016 High

    Conditional knockdown established RIPR as strictly essential and placed the RCR complex upstream of tight-junction formation and host Ca2+ signalling during invasion.

    Evidence Conditional knockdown, STED super-resolution colocalization, Ca2+ flux and invasion assays in P. falciparum

    PMID:27374406

    Open questions at the time
    • Direct trigger of Ca2+ release not defined at molecular level
    • Individual contribution of RIPR versus other complex members to junction formation unclear
  4. 2017 Medium

    Systematic interaction mapping and P113 studies defined the binding interdependencies of RIPR within the RH5 complex and an additional releasable surface-anchoring route via P113–RH5.

    Evidence AVEXIS recombinant protein interaction screen in P. falciparum

    PMID:28186186

    Open questions at the time
    • RIPR does not bind P113 directly, so its own anchoring path remained partly unresolved
    • In vitro AVEXIS interactions not confirmed in native parasite context
  5. 2017 Medium

    Domain-mapping localized a neutralizing epitope to RIPR EGF-7 acting downstream of complex assembly and showed anti-RIPR/anti-CyRPA antibody synergy, focusing vaccine efforts on RIPR's C-terminal region.

    Evidence Recombinant RIPR fragment domain-mapping and antibody invasion inhibition/synergy assays in P. falciparum

    PMID:30965383

    Open questions at the time
    • Mechanism of downstream inhibition not resolved structurally
    • Single-lab epitope assignment
  6. 2018 High

    Cryo-EM of the Rh5–CyRPA–RIPR complex defined CyRPA as the assembly hub and showed the intact complex binds and inserts into erythrocyte membranes better than Rh5 alone, explaining RIPR's role in host membrane engagement.

    Evidence Sub-nanometre cryo-EM, erythrocyte-binding and membrane-insertion assays in P. falciparum

    PMID:30542156

    Open questions at the time
    • High-resolution architecture of RIPR itself not resolved in this map
    • Physiological trigger for proposed Rh5/RIPR dissociation from CyRPA not defined
  7. 2019 Medium

    Antibodies against the C-terminal PfRipr_5 fragment simultaneously blocked the RIPR/Rh5 interaction and a RIPR–SEMA7A erythrocyte-receptor interaction, implicating RIPR's C-terminus in both complex assembly and host receptor engagement.

    Evidence Cell-free expressed RIPR truncates, invasion inhibition, and protein-interaction blocking assays in P. falciparum

    PMID:32313230

    Open questions at the time
    • Functional relevance of the RIPR–SEMA7A interaction during invasion not established genetically
    • Single-lab interaction assignment
  8. 2019 Medium

    Study of the P. knowlesi ortholog showed RIPR's essentiality for invasion is conserved but its complex partners are not, revealing an RH5/CyRPA-independent function outside Laverania.

    Evidence Conditional knockdown, Co-IP/pull-down, and invasion assays in P. knowlesi

    PMID:31185066

    Open questions at the time
    • Identity of the alternative PkRIPR trimeric complex partners not fully defined
    • Molecular role of PkRIPR in its distinct complex unknown
  9. 2022 High

    Defining the pentameric PCRCR complex placed RIPR within a membrane-anchored assembly (PfPTRAMP–PfCSS–RIPR–CyRPA–Rh5) that stabilizes merozoite–erythrocyte membrane contact during invasion.

    Evidence Conditional knockouts, nanobody inhibition, lattice light-sheet microscopy, and cryo-EM in P. falciparum

    PMID:36396942

    Open questions at the time
    • Direct RIPR–PfPTRAMP/PfCSS contact not structurally resolved in this study
    • Temporal order of PCRCR assembly during invasion unclear
  10. 2023 High

    Cryo-EM of the RCR complex resolved RIPR's architecture—a structured core with a flexible elongated tail—and showed the tail binds PfCSS–PfPTRAMP, defining RIPR as the physical link between the merozoite membrane and the erythrocyte-engaging Rh5/CyRPA module.

    Evidence Cryo-EM structure determination, erythrocyte-binding assay, and interaction modelling in P. falciparum

    PMID:38123677

    Open questions at the time
    • Dynamics of tail–membrane engagement during invasion not directly observed
    • Conformational changes upon receptor binding not resolved
  11. 2024 Medium

    Mapping all growth-inhibitory epitopes to RIPR's C-terminal EGF-like domains, and fusing them to CyRPA (R78C) to enhance inhibition, validated this region as the functionally critical vaccine target of RIPR.

    Evidence Monoclonal antibody epitope mapping, invasion inhibition, and rat immunization in P. falciparum

    PMID:38849365

    Open questions at the time
    • Protective efficacy in vivo not established
    • Structural basis of neutralization in this fusion not resolved
  12. 2026 High

    Cross-species reconstitution defined a conserved PTRAMP–CSS–RIPR (PCR) core built on disulfide-linked PTRAMP–CSS heterodimers binding RIPR's C-terminus, and identified a cross-reactive inhibitory antibody epitope on the RIPR C-terminal tail.

    Evidence Multi-species biochemical reconstitution, disulfide analysis, invasion inhibition, and crystal structure of antibody–PvRipr tail in P. falciparum, P. vivax, and P. knowlesi

    PMID:41587959

    Open questions at the time
    • Whether the conserved PCR core assembles identically in vivo across species not shown
    • Cross-species neutralization breadth in vivo not established
  13. 2026 High

    Fine epitope mapping and human mAb structural studies defined the mechanism of anti-RIPR neutralization: antibodies to the EGF6–8 tail constrain RIPR conformation and dissociate PfPTRAMP–CSS, enabling synergistic potentiation by antibodies to other RIPR domains or CSS.

    Evidence Cysteine-substitution/SPR epitope mapping and human mAb panel with cryo-EM/crystallography, MD simulation, and dissociation/synergy assays in P. falciparum

    PMID:41676142 PMID:42285102

    Open questions at the time
    • Protective correlates of the synergistic mAb combinations in vivo not established
    • Native conformational dynamics of RIPR during invasion not directly captured

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RIPR mechanistically triggers erythrocyte Ca2+ release, whether its structured core directly engages a host receptor during productive invasion, and the identity of its distinct non-Laverania complex partners remain unresolved.
  • Molecular link between RCR/PCRCR engagement and host Ca2+ signalling undefined
  • In vivo role of the RIPR–SEMA7A interaction untested genetically
  • Composition of the P. knowlesi PkRIPR trimeric complex incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
CYRPAP113 (INDIRECT, VIA RH5)PFCSSPFPTRAMPPFRH5SEMA7A (ERYTHROCYTE RECEPTOR)
Complex memberships
Distinct trimeric PkRIPR complex (P. knowlesi, CyRPA/RH5-independent)PCR complex (PTRAMP–CSS–RIPR)PCRCR complex (PfPTRAMP–PfCSS–RIPR–CyRPA–Rh5)RCR complex (PfRh5–CyRPA–RIPR)

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 RIPR (PfRipr, PFC1045c) was identified as a novel cysteine-rich protein that forms a complex with PfRh5 in merozoites. RIPR has a molecular weight of ~123 kDa with 10 EGF-like domains and 87 cysteine residues; in mature schizonts it is processed into two polypeptides that associate and form a complex with PfRh5. RIPR localizes to the apical end of merozoites in micronemes, while PfRh5 is in rhoptries; both are released during invasion and the complex is shed into culture supernatant. Antibodies to RIPR potently inhibit merozoite attachment and invasion into human red blood cells. Ion-exchange chromatography, immunoprecipitation, mass spectrometry, immunofluorescence localization, antibody-based invasion inhibition assay PLoS pathogens High 21909261
2015 RIPR (PfRipr) together with PfRh5 and the GPI-anchored protein CyRPA forms a multiprotein complex on the merozoite surface. CyRPA, which lacks a transmembrane domain, was shown by co-immunoprecipitation to interact with both PfRh5 and RIPR, and specific antibodies against all three proteins detected the intact complex in the parasite. CyRPA provides the GPI-anchored membrane tether for the PfRh5/RIPR/CyRPA complex, explaining how RIPR (which lacks transmembrane domains and GPI anchors) is anchored to the merozoite surface. Co-immunoprecipitation of native parasite complex, GPI-linkage biochemical assay, immunofluorescence localization Proceedings of the National Academy of Sciences of the United States of America High 25583518
2016 Loss of RIPR (PfRipr) function by conditional expression knockdown blocks erythrocyte invasion by P. falciparum merozoites. Super-resolution microscopy revealed that RIPR colocalizes with CyRPA and PfRh5 at the junction between merozoites and erythrocytes during invasion. The PfRh5/RIPR/CyRPA complex is required for triggering Ca2+ release in the erythrocyte and for establishing the tight junction during invasion. Conditional knockdown of PfRipr in P. falciparum, super-resolution microscopy (STED), Ca2+ flux assay, invasion assay Cell host & microbe High 27374406
2018 Cryo-electron microscopy of the Rh5-CyRPA-RIPR complex at sub-nanometre resolution revealed that CyRPA is a critical mediator of complex assembly, with blades 4–6 of the CyRPA β-propeller serving as contact sites for both Rh5 and RIPR. The complex binds the erythrocyte line JK-1 significantly better than Rh5 alone, and Rh5 and RIPR insert into host membranes as a high-molecular-weight complex. Limited contacts between Rh5-CyRPA and CyRPA-RIPR are consistent with dissociation of Rh5 and RIPR from CyRPA for membrane insertion. Cryo-electron microscopy (sub-nanometre resolution), erythrocyte-binding assay with intact complex vs Rh5 alone, membrane insertion assay Nature High 30542156
2017 Antibodies against RIPR identify the EGF-7 domain as a neutralizing epitope; antibodies against this region act downstream of complex formation to prevent merozoite invasion. Antibodies against the C-terminal region of RIPR were more inhibitory than those against either PfRh5 or CyRPA alone, and a combination of anti-CyRPA and anti-RIPR antibodies acts synergistically to reduce invasion. Domain-mapping with recombinant RIPR fragments, antibody-based invasion inhibition assay, antibody combination synergy assay Cellular microbiology Medium 30965383
2019 Antibodies against RIPR truncate 5 (PfRipr_5: residues C720–D934, within the C-terminal EGF-like domains) potently inhibit merozoite invasion and strongly block both the PfRipr/Rh5 interaction and the interaction between RIPR and its erythrocyte-surface receptor SEMA7A. Wheat germ cell-free expression of RIPR truncates, antibody-based invasion inhibition assay, protein–protein interaction blocking assay (RIPR/Rh5 and RIPR/SEMA7A) Scientific reports Medium 32313230
2017 RIPR (referred to as part of the RH5 complex) interacts with P113 indirectly through RH5: P113 is a merozoite surface protein that binds the conserved N-terminal region of RH5 (RH5Nt), and this interaction provides a releasable mechanism for anchoring the RH5 complex (including RIPR) to the merozoite surface. Binding interdependencies of all known RH5 complex components including RIPR were established using recombinant proteins and a sensitive protein interaction assay. Recombinant protein interaction assay (AVEXIS), systematic binding interdependency mapping of complex components Nature communications Medium 28186186
2022 RIPR (PfRipr) is a component of the larger pentameric PCRCR complex (PfPTRAMP–PfCSS–PfRipr–CyRPA–Rh5). The PfPTRAMP/PfCSS heterodimeric complex binds to the RCR complex (which includes RIPR) to form PCRCR. Conditional knockouts and lattice light-sheet microscopy showed that the PCRCR complex functions to anchor the contact between merozoite and erythrocyte membranes during invasion. Conditional knockout of PCRCR components in P. falciparum, nanobody inhibition of PfCSS and PfPTRAMP, lattice light-sheet microscopy, cryo-EM structure of nanobody-PfCSS complexes Nature microbiology High 36396942
2023 Cryo-EM structure of the PfRCR complex (Rh5–CyRPA–RIPR) showed that RIPR consists of an ordered multidomain core flexibly linked to an elongated tail. The elongated tail of RIPR, which is the target of growth-neutralizing antibodies, binds to the PfCSS–PfPTRAMP complex on the parasite membrane. RIPR thus links the merozoite membrane through its elongated tail while its structured core presents CyRPA and Rh5 to interact with erythrocyte receptors. Cryo-EM structure determination of RCR complex, erythrocyte-binding assay, modelling of RIPR tail–PfCSS/PfPTRAMP interaction Nature High 38123677
2019 In P. knowlesi, the RIPR ortholog (PkRIPR) is essential for erythrocyte invasion but does not form a complex with PkCyRPA or with an RH5-like molecule. Instead, PkRIPR is part of a different trimeric protein complex. This demonstrates that outside the Laverania subgenus, in the absence of RH5, RIPR has an independent function from CyRPA, distinct from its role in P. falciparum. Conditional knockdown of PkRipr in P. knowlesi, Co-IP/pull-down to test complex formation with PkCyRPA, invasion assays PLoS pathogens Medium 31185066
2024 All growth-inhibitory antibody epitopes of RIPR cluster within the C-terminal EGF-like domains. A fusion of these domains to CyRPA (called 'R78C'), combined with RH5, improves in vitro parasite growth inhibition compared to RH5 alone, supporting RIPR's C-terminal EGF domains as the functionally critical vaccine target region. Monoclonal antibody epitope mapping, invasion inhibition assay, rat immunization with RCR-complex and component antigens Nature communications Medium 38849365
2026 RIPR (PfRipr) within the PCRCR complex is conserved across Plasmodium species. In P. vivax and P. knowlesi, PTRAMP and CSS form disulfide-linked heterodimers that complex with RIPR via its C-terminal region, forming the PCR (PTRAMP-CSS-Ripr) complex. Cross-reactive antibodies targeting the PCR complex inhibit merozoite invasion, and a crystal structure of a cross-reactive antibody revealed an inhibitory epitope on the C-terminal tail of PvRipr. Biochemical complex reconstitution across three Plasmodium species, disulfide linkage analysis, invasion inhibition assays with cross-reactive antibodies, crystal structure of antibody-PvRipr C-terminal tail complex Nature communications High 41587959
2026 A growth-inhibitory monoclonal antibody (29B11) against RIPR fragment PfRipr5 (EGF-like domains 5–9) recognizes a specific 20-amino-acid cysteine-associated epitope within PfRipr5, as mapped by Western blotting with cysteine-substituted mutants and surface plasmon resonance. Integrity of the cysteine residues in this epitope is required for antibody recognition. Cysteine-substitution mutagenesis, Western blotting, surface plasmon resonance (SPR) epitope mapping Frontiers in immunology Medium 41676142
2026 Pools of human monoclonal antibodies (mAbs) targeting the RIPR-tail region (EGF-like domains 6–8) show high-level synergistic invasion inhibition, while single mAbs have minimal neutralizing activity. Structural characterization and molecular dynamics simulations showed that mAbs targeting RIPREGF(6–8) constrain the RIPR-tail conformation and cause dissociation of PfPTRAMP-CSS from RIPR, enabling additional anti-RIPR mAbs targeting other domains (RIPREGF(9–10)/CTD) or anti-CSS antibodies to potentiate growth inhibition. Human mAb characterization (83 mAbs), invasion inhibition synergy assay, cryo-EM/crystallography of RIPR-tail, molecular dynamics simulation, dissociation assay of RIPR–PfPTRAMP-CSS interaction Immunity High 42285102

Source papers

Stage 0 corpus · 86 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum. Nature 528 22080952
2015 Revealing the sequence and resulting cellular morphology of receptor-ligand interactions during Plasmodium falciparum invasion of erythrocytes. PLoS pathogens 236 25723550
2011 The blood-stage malaria antigen PfRH5 is susceptible to vaccine-inducible cross-strain neutralizing antibody. Nature communications 229 22186897
2008 Reticulocyte-binding protein homologue 5 - an essential adhesin involved in invasion of human erythrocytes by Plasmodium falciparum. International journal for parasitology 208 19000690
2008 Erythrocyte binding protein PfRH5 polymorphisms determine species-specific pathways of Plasmodium falciparum invasion. Cell host & microbe 205 18621009
2014 Structure of malaria invasion protein RH5 with erythrocyte basigin and blocking antibodies. Nature 184 25132548
2015 A PfRH5-based vaccine is efficacious against heterologous strain blood-stage Plasmodium falciparum infection in aotus monkeys. Cell host & microbe 178 25590760
2016 Essential Role of the PfRh5/PfRipr/CyRPA Complex during Plasmodium falciparum Invasion of Erythrocytes. Cell host & microbe 163 27374406
2015 Multiprotein complex between the GPI-anchored CyRPA with PfRH5 and PfRipr is crucial for Plasmodium falciparum erythrocyte invasion. Proceedings of the National Academy of Sciences of the United States of America 144 25583518
2014 Plasmodium falciparum erythrocyte invasion: combining function with immune evasion. PLoS pathogens 131 24651270
2011 An EGF-like protein forms a complex with PfRh5 and is required for invasion of human erythrocytes by Plasmodium falciparum. PLoS pathogens 131 21909261
2019 Human Antibodies that Slow Erythrocyte Invasion Potentiate Malaria-Neutralizing Antibodies. Cell 124 31204103
2013 Neutralization of Plasmodium falciparum merozoites by antibodies against PfRH5. Journal of immunology (Baltimore, Md. : 1950) 123 24293631
2021 Reduced blood-stage malaria growth and immune correlates in humans following RH5 vaccination. Med (New York, N.Y.) 118 34223402
2012 A full-length recombinant Plasmodium falciparum PfRH5 protein induces inhibitory antibodies that are effective across common PfRH5 genetic variants. Vaccine 115 23146673
2012 Enhancing blockade of Plasmodium falciparum erythrocyte invasion: assessing combinations of antibodies against PfRH5 and other merozoite antigens. PLoS pathogens 112 23144611
2017 Human vaccination against RH5 induces neutralizing antimalarial antibodies that inhibit RH5 invasion complex interactions. JCI insight 110 29093263
2013 Naturally acquired antibodies specific for Plasmodium falciparum reticulocyte-binding protein homologue 5 inhibit parasite growth and predict protection from malaria. The Journal of infectious diseases 100 24133188
2013 RH5-Basigin interaction plays a major role in the host tropism of Plasmodium falciparum. Proceedings of the National Academy of Sciences of the United States of America 98 24297912
2015 Recent advances in recombinant protein-based malaria vaccines. Vaccine 92 26458807
2018 Structure of Plasmodium falciparum Rh5-CyRPA-Ripr invasion complex. Nature 84 30542156
2008 PfRH5: a novel reticulocyte-binding family homolog of plasmodium falciparum that binds to the erythrocyte, and an investigation of its receptor. PloS one 79 18827878
2017 One-step design of a stable variant of the malaria invasion protein RH5 for use as a vaccine immunogen. Proceedings of the National Academy of Sciences of the United States of America 73 28096331
2013 Bacterially expressed full-length recombinant Plasmodium falciparum RH5 protein binds erythrocytes and elicits potent strain-transcending parasite-neutralizing antibodies. Infection and immunity 70 24126527
2015 Host-parasite interactions that guide red blood cell invasion by malaria parasites. Current opinion in hematology 63 25767956
2017 P113 is a merozoite surface protein that binds the N terminus of Plasmodium falciparum RH5. Nature communications 59 28186186
2017 Structure of the malaria vaccine candidate antigen CyRPA and its complex with a parasite invasion inhibitory antibody. eLife 59 28195038
2014 Crystal structure of PfRh5, an essential P. falciparum ligand for invasion of human erythrocytes. eLife 59 25296023
2010 Erythrocyte invasion and merozoite ligand gene expression in severe and mild Plasmodium falciparum malaria. The Journal of infectious diseases 59 20050806
2022 PCRCR complex is essential for invasion of human erythrocytes by Plasmodium falciparum. Nature microbiology 58 36396942
2019 A defined mechanistic correlate of protection against Plasmodium falciparum malaria in non-human primates. Nature communications 58 31028254
2018 Production, quality control, stability, and potency of cGMP-produced Plasmodium falciparum RH5.1 protein vaccine expressed in Drosophila S2 cells. NPJ vaccines 58 30131879
2013 Plasmodium falciparum merozoite surface antigen, PfRH5, elicits detectable levels of invasion-inhibiting antibodies in humans. The Journal of infectious diseases 56 23904294
2020 The RH5-CyRPA-Ripr Complex as a Malaria Vaccine Target. Trends in parasitology 55 32359873
2017 Accelerating the clinical development of protein-based vaccines for malaria by efficient purification using a four amino acid C-terminal 'C-tag'. International journal for parasitology 55 28153778
2021 Human Basigin (CD147) Does Not Directly Interact with SARS-CoV-2 Spike Glycoprotein. mSphere 54 34378982
2017 Structural basis for inhibition of erythrocyte invasion by antibodies to Plasmodium falciparum protein CyRPA. eLife 53 28195530
2017 CRISPR/Cas9 knockouts reveal genetic interaction between strain-transcendent erythrocyte determinants of Plasmodium falciparum invasion. Proceedings of the National Academy of Sciences of the United States of America 53 29078358
2015 Basigin is a druggable target for host-oriented antimalarial interventions. The Journal of experimental medicine 53 26195724
2016 The association between naturally acquired IgG subclass specific antibodies to the PfRH5 invasion complex and protection from Plasmodium falciparum malaria. Scientific reports 52 27604417
2019 Antibody responses to merozoite antigens after natural Plasmodium falciparum infection: kinetics and longevity in absence of re-exposure. BMC medicine 51 30696449
2016 Production of full-length soluble Plasmodium falciparum RH5 protein vaccine using a Drosophila melanogaster Schneider 2 stable cell line system. Scientific reports 50 27457156
2015 Structurally conserved erythrocyte-binding domain in Plasmodium provides a versatile scaffold for alternate receptor engagement. Proceedings of the National Academy of Sciences of the United States of America 49 26715754
2014 A malaria vaccine candidate based on an epitope of the Plasmodium falciparum RH5 protein. Malaria journal 48 25135070
2019 Neutralising antibodies block the function of Rh5/Ripr/CyRPA complex during invasion of Plasmodium falciparum into human erythrocytes. Cellular microbiology 47 30965383
2015 Progress with viral vectored malaria vaccines: A multi-stage approach involving "unnatural immunity". Vaccine 45 26476366
2021 Protein/AS01B vaccination elicits stronger, more Th2-skewed antigen-specific human T follicular helper cell responses than heterologous viral vectors. Cell reports. Medicine 43 33763653
2022 Global diversity and balancing selection of 23 leading Plasmodium falciparum candidate vaccine antigens. PLoS computational biology 42 35108259
2014 Association of antibodies to Plasmodium falciparum reticulocyte binding protein homolog 5 with protection from clinical malaria. Frontiers in microbiology 41 25071730
2019 Divergent roles for the RH5 complex components, CyRPA and RIPR in human-infective malaria parasites. PLoS pathogens 40 31185066
2019 Functional Comparison of Blood-Stage Plasmodium falciparum Malaria Vaccine Candidate Antigens. Frontiers in immunology 38 31214195
2015 Variation in Plasmodium falciparum erythrocyte invasion phenotypes and merozoite ligand gene expression across different populations in areas of malaria endemicity. Infection and immunity 37 25870227
2024 Blood-stage malaria vaccine candidate RH5.1/Matrix-M in healthy Tanzanian adults and children; an open-label, non-randomised, first-in-human, single-centre, phase 1b trial. The Lancet. Infectious diseases 36 38880111
2019 Resurrection of the ancestral RH5 invasion ligand provides a molecular explanation for the origin of P. falciparum malaria in humans. PLoS biology 36 31613878
2017 P. falciparum RH5-Basigin interaction induces changes in the cytoskeleton of the host RBC. Cellular microbiology 36 28409866
2012 Targeting sialic acid dependent and independent pathways of invasion in Plasmodium falciparum. PloS one 35 22253925
2015 Analysis of Erythrocyte Invasion Mechanisms of Plasmodium falciparum Clinical Isolates Across 3 Malaria-Endemic Areas in Ghana. The Journal of infectious diseases 34 25838264
2018 Kinetics of antibody responses to PfRH5-complex antigens in Ghanaian children with Plasmodium falciparum malaria. PloS one 33 29883485
2013 Identifying novel Plasmodium falciparum erythrocyte invasion receptors using systematic extracellular protein interaction screens. Cellular microbiology 33 23617720
2023 The PfRCR complex bridges malaria parasite and erythrocyte during invasion. Nature 32 38123677
2016 Identification of Plasmodium falciparum reticulocyte binding protein homologue 5-interacting protein, PfRipr, as a highly conserved blood-stage malaria vaccine candidate. Vaccine 32 27692771
2012 Anti-Plasmodium falciparum invasion ligand antibodies in a low malaria transmission region, Loreto, Peru. Malaria journal 32 23110555
2024 Safety and efficacy of the blood-stage malaria vaccine RH5.1/Matrix-M in Burkina Faso: interim results of a double-blind, randomised, controlled, phase 2b trial in children. The Lancet. Infectious diseases 31 39672183
2023 Superior antibody immunogenicity of a viral-vectored RH5 blood-stage malaria vaccine in Tanzanian infants as compared to adults. Med (New York, N.Y.) 29 37572659
2012 Basigin: a multifunctional membrane protein with an emerging role in infections by malaria parasites. Expert opinion on therapeutic targets 29 22880881
2024 Development of an improved blood-stage malaria vaccine targeting the essential RH5-CyRPA-RIPR invasion complex. Nature communications 27 38849365
2020 Bliss' and Loewe's additive and synergistic effects in Plasmodium falciparum growth inhibition by AMA1-RON2L, RH5, RIPR and CyRPA antibody combinations. Scientific reports 27 32678144
2013 Various PfRH5 polymorphisms can support Plasmodium falciparum invasion into the erythrocytes of owl monkeys and rats. Molecular and biochemical parasitology 27 23305874
2024 Vaccines and monoclonal antibodies: new tools for malaria control. Clinical microbiology reviews 26 38656211
2020 Antibodies against a short region of PfRipr inhibit Plasmodium falciparum merozoite invasion and PfRipr interaction with Rh5 and SEMA7A. Scientific reports 26 32313230
2018 KILchip v1.0: A Novel Plasmodium falciparum Merozoite Protein Microarray to Facilitate Malaria Vaccine Candidate Prioritization. Frontiers in immunology 26 30619257
2012 Plasmodium falciparum field isolates from South America use an atypical red blood cell invasion pathway associated with invasion ligand polymorphisms. PloS one 26 23118907
2024 Analysis of the diverse antigenic landscape of the malaria protein RH5 identifies a potent vaccine-induced human public antibody clonotype. Cell 24 39059380
2020 Genetic polymorphisms in malaria vaccine candidate Plasmodium falciparum reticulocyte-binding protein homologue-5 among populations in Lagos, Nigeria. Malaria journal 23 31906953
2020 Antibody responses to the RTS,S/AS01E vaccine and Plasmodium falciparum antigens after a booster dose within the phase 3 trial in Mozambique. NPJ vaccines 23 32550014
2024 Preclinical development of a stabilized RH5 virus-like particle vaccine that induces improved antimalarial antibodies. Cell reports. Medicine 21 39019011
2021 The Plasmodium falciparum Rh5 invasion protein complex reveals an excess of rare variant mutations. Malaria journal 21 34162366
2018 Shed EBA-175 mediates red blood cell clustering that enhances malaria parasite growth and enables immune evasion. eLife 21 30556808
2026 PTRAMP, CSS and Ripr form a conserved complex required for merozoite invasion of Plasmodium species into erythrocytes. Nature communications 2 41587959
2026 Identification of a growth-inhibitory epitope in PfRipr5, a malaria vaccine candidate against Plasmodium falciparum. Frontiers in immunology 2 41676142
2026 Genetic diversity of the malaria vaccine candidate PfRIPR in a high transmission region of Senegal. iScience 1 41736865
2026 B and T cell responses to pre-erythrocytic R21/Matrix-M and blood-stage RH5.1/Matrix-M malaria vaccines in endemic settings. Frontiers in immunology 1 41846927
2026 Assessing the effect of parasite antigen genetic diversity on performance of Plasmodium vivax serological exposure markers for malaria: a multicentre observational diagnostic accuracy study. The Lancet. Microbe 1 42155491
2026 B-cell epitope mapping and characterization of antibody responses to recombinant PvRipr in malaria-exposed individuals. Frontiers in immunology 0 41684541
2026 Unraveling the genetic diversity of RIPR, a key invasion protein in Plasmodium vivax malaria. Parasitology 0 42187229
2026 Analysis of monoclonal antibodies against the malaria invasion complex protein RIPR reveals the structural basis for synergistic antibody protection. Immunity 0 42285102