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Neutralising antibodies block the function of Rh5/Ripr/CyRPA complex during invasion of Plasmodium falciparum into human erythrocytes.
Healer, Julie; Wong, Wilson; Thompson, Jennifer K; He, Wengqiang; Birkinshaw, Richard W; Miura, Kazutoyo; Long, Carol A; Soroka, Vladislav; Søgaard, Teit Max Moscote; Jørgensen, Thomas; de Jongh, Willem A; Weir, Christopher; Svahn, Ella; Czabotar, Peter E; Tham, Wai-Hong; Mueller, Ivo; Barlow, Paul N; Cowman, Alan F.
Affiliation
  • Healer J; Infection and Immunity, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
  • Wong W; Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia.
  • Thompson JK; Infection and Immunity, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
  • He W; Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia.
  • Birkinshaw RW; Infection and Immunity, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
  • Miura K; Infection and Immunity, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
  • Long CA; Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia.
  • Soroka V; Infection and Immunity, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
  • Søgaard TMM; Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia.
  • Jørgensen T; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • de Jongh WA; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Weir C; ExpreS2ion Biotechnologies, Horsholm, Denmark.
  • Svahn E; ExpreS2ion Biotechnologies, Horsholm, Denmark.
  • Czabotar PE; ExpreS2ion Biotechnologies, Horsholm, Denmark.
  • Tham WH; ExpreS2ion Biotechnologies, Horsholm, Denmark.
  • Mueller I; Infection and Immunity, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
  • Barlow PN; Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia.
  • Cowman AF; Schools of Chemistry and Biological Sciences, University of Edinburgh, Edinburgh, Scotland, UK.
Cell Microbiol ; 21(7): e13030, 2019 07.
Article in En | MEDLINE | ID: mdl-30965383
ABSTRACT
An effective vaccine is a priority for malaria control and elimination. The leading candidate in the Plasmodium falciparum blood stage is PfRh5. PfRh5 assembles into trimeric complex with PfRipr and PfCyRPA in the parasite, and this complex is essential for erythrocyte invasion. In this study, we show that antibodies specific for PfRh5 and PfCyRPA prevent trimeric complex formation. We identify the EGF-7 domain on PfRipr as a neutralising epitope and demonstrate that antibodies against this region act downstream of complex formation to prevent merozoite invasion. Antibodies against the C-terminal region of PfRipr were more inhibitory than those against either PfRh5 or PfCyRPA alone, and a combination of antibodies against PfCyRPA and PfRipr acted synergistically to reduce invasion. This study supports prioritisation of PfRipr for development as part of a next-generation antimalarial vaccine.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Carrier Proteins / Protozoan Proteins / Malaria, Falciparum / Antibodies, Neutralizing / Antigens, Protozoan Limits: Humans Language: En Journal: Cell Microbiol Journal subject: MICROBIOLOGIA Year: 2019 Type: Article Affiliation country: Australia
Fulltext
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PubMed Links
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Carrier Proteins / Protozoan Proteins / Malaria, Falciparum / Antibodies, Neutralizing / Antigens, Protozoan Limits: Humans Language: En Journal: Cell Microbiol Journal subject: MICROBIOLOGIA Year: 2019 Type: Article Affiliation country: Australia