Your browser doesn't support javascript.
loading
Development of an improved blood-stage malaria vaccine targeting the essential RH5-CyRPA-RIPR invasion complex.
Williams, Barnabas G; King, Lloyd D W; Pulido, David; Quinkert, Doris; Lias, Amelia M; Silk, Sarah E; Ragotte, Robert J; Davies, Hannah; Barrett, Jordan R; McHugh, Kirsty; Rigby, Cassandra A; Alanine, Daniel G W; Barfod, Lea; Shea, Michael W; Cowley, Li An; Dabbs, Rebecca A; Pattinson, David J; Douglas, Alexander D; Lyth, Oliver R; Illingworth, Joseph J; Jin, Jing; Carnrot, Cecilia; Kotraiah, Vinayaka; Christen, Jayne M; Noe, Amy R; MacGill, Randall S; King, C Richter; Birkett, Ashley J; Soisson, Lorraine A; Skinner, Katherine; Miura, Kazutoyo; Long, Carole A; Higgins, Matthew K; Draper, Simon J.
Afiliación
  • Williams BG; Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford, UK.
  • King LDW; Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, Oxford, UK.
  • Pulido D; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford, UK.
  • Quinkert D; Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford, UK.
  • Lias AM; Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, Oxford, UK.
  • Silk SE; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford, UK.
  • Ragotte RJ; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford, UK.
  • Davies H; Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford, UK.
  • Barrett JR; Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, Oxford, UK.
  • McHugh K; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford, UK.
  • Rigby CA; Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford, UK.
  • Alanine DGW; Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, Oxford, UK.
  • Barfod L; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford, UK.
  • Shea MW; Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford, UK.
  • Cowley LA; Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, Oxford, UK.
  • Dabbs RA; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford, UK.
  • Pattinson DJ; Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford, UK.
  • Douglas AD; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford, UK.
  • Lyth OR; Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford, UK.
  • Illingworth JJ; Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, Oxford, UK.
  • Jin J; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford, UK.
  • Carnrot C; Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford, UK.
  • Kotraiah V; Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, Oxford, UK.
  • Christen JM; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford, UK.
  • Noe AR; Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford, UK.
  • MacGill RS; Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, Oxford, UK.
  • King CR; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford, UK.
  • Birkett AJ; Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford, UK.
  • Soisson LA; Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, Oxford, UK.
  • Skinner K; Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford, UK.
  • Miura K; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford, UK.
  • Long CA; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford, UK.
  • Higgins MK; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford, UK.
  • Draper SJ; Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford, UK.
Nat Commun ; 15(1): 4857, 2024 Jun 07.
Article en En | MEDLINE | ID: mdl-38849365
ABSTRACT
Reticulocyte-binding protein homologue 5 (RH5), a leading blood-stage Plasmodium falciparum malaria vaccine target, interacts with cysteine-rich protective antigen (CyRPA) and RH5-interacting protein (RIPR) to form an essential heterotrimeric "RCR-complex". We investigate whether RCR-complex vaccination can improve upon RH5 alone. Using monoclonal antibodies (mAbs) we show that parasite growth-inhibitory epitopes on each antigen are surface-exposed on the RCR-complex and that mAb pairs targeting different antigens can function additively or synergistically. However, immunisation of female rats with the RCR-complex fails to outperform RH5 alone due to immuno-dominance of RIPR coupled with inferior potency of anti-RIPR polyclonal IgG. We identify that all growth-inhibitory antibody epitopes of RIPR cluster within the C-terminal EGF-like domains and that a fusion of these domains to CyRPA, called "R78C", combined with RH5, improves the level of in vitro parasite growth inhibition compared to RH5 alone. These preclinical data justify the advancement of the RH5.1 + R78C/Matrix-M™ vaccine candidate to Phase 1 clinical trial.
Asunto(s)
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Plasmodium falciparum / Anticuerpos Antiprotozoarios / Proteínas Protozoarias / Malaria Falciparum / Vacunas contra la Malaria / Anticuerpos Monoclonales / Antígenos de Protozoos Límite: Animals / Female / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Reino Unido
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Plasmodium falciparum / Anticuerpos Antiprotozoarios / Proteínas Protozoarias / Malaria Falciparum / Vacunas contra la Malaria / Anticuerpos Monoclonales / Antígenos de Protozoos Límite: Animals / Female / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Reino Unido