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Structural basis for inhibition of Plasmodium vivax invasion by a broadly neutralizing vaccine-induced human antibody.
Rawlinson, Thomas A; Barber, Natalie M; Mohring, Franziska; Cho, Jee Sun; Kosaisavee, Varakorn; Gérard, Samuel F; Alanine, Daniel G W; Labbé, Geneviève M; Elias, Sean C; Silk, Sarah E; Quinkert, Doris; Jin, Jing; Marshall, Jennifer M; Payne, Ruth O; Minassian, Angela M; Russell, Bruce; Rénia, Laurent; Nosten, François H; Moon, Robert W; Higgins, Matthew K; Draper, Simon J.
Afiliación
  • Rawlinson TA; Jenner Institute, University of Oxford, Oxford, UK.
  • Barber NM; Department of Biochemistry, University of Oxford, Oxford, UK.
  • Mohring F; Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
  • Cho JS; Jenner Institute, University of Oxford, Oxford, UK.
  • Kosaisavee V; Faculty of Public Health, Mahidol University, Bangkok, Thailand.
  • Gérard SF; Department of Biochemistry, University of Oxford, Oxford, UK.
  • Alanine DGW; Jenner Institute, University of Oxford, Oxford, UK.
  • Labbé GM; Jenner Institute, University of Oxford, Oxford, UK.
  • Elias SC; Jenner Institute, University of Oxford, Oxford, UK.
  • Silk SE; Jenner Institute, University of Oxford, Oxford, UK.
  • Quinkert D; Jenner Institute, University of Oxford, Oxford, UK.
  • Jin J; Jenner Institute, University of Oxford, Oxford, UK.
  • Marshall JM; Jenner Institute, University of Oxford, Oxford, UK.
  • Payne RO; Jenner Institute, University of Oxford, Oxford, UK.
  • Minassian AM; Jenner Institute, University of Oxford, Oxford, UK.
  • Russell B; Department of Microbiology and Immunology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.
  • Rénia L; Singapore Immunology Network, A*STAR, Singapore, Singapore.
  • Nosten FH; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Moon RW; Shoklo Malaria Research Unit, Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
  • Higgins MK; Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
  • Draper SJ; Department of Biochemistry, University of Oxford, Oxford, UK. matthew.higgins@bioch.ox.ac.uk.
Nat Microbiol ; 4(9): 1497-1507, 2019 09.
Article en En | MEDLINE | ID: mdl-31133755
The most widespread form of malaria is caused by Plasmodium vivax. To replicate, this parasite must invade immature red blood cells through a process requiring interaction of the P. vivax Duffy binding protein (PvDBP) with its human receptor, the Duffy antigen receptor for chemokines. Naturally acquired antibodies that inhibit this interaction associate with clinical immunity, suggesting PvDBP as a leading candidate for inclusion in a vaccine to prevent malaria due to P. vivax. Here, we isolated a panel of monoclonal antibodies from human volunteers immunized in a clinical vaccine trial of PvDBP. We screened their ability to prevent PvDBP from binding to the Duffy antigen receptor for chemokines, and their capacity to block red blood cell invasion by a transgenic Plasmodium knowlesi parasite genetically modified to express PvDBP and to prevent reticulocyte invasion by multiple clinical isolates of P. vivax. This identified a broadly neutralizing human monoclonal antibody that inhibited invasion of all tested strains of P. vivax. Finally, we determined the structure of a complex of this antibody bound to PvDBP, indicating the molecular basis for inhibition. These findings will guide future vaccine design strategies and open up possibilities for testing the prophylactic use of such an antibody.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plasmodium vivax / Anticuerpos Antiprotozoarios / Proteínas Protozoarias / Malaria Vivax / Vacunas contra la Malaria / Receptores de Superficie Celular / Antígenos de Protozoos Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Nat Microbiol Año: 2019 Tipo del documento: Article Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plasmodium vivax / Anticuerpos Antiprotozoarios / Proteínas Protozoarias / Malaria Vivax / Vacunas contra la Malaria / Receptores de Superficie Celular / Antígenos de Protozoos Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Nat Microbiol Año: 2019 Tipo del documento: Article Pais de publicación: Reino Unido