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A human monoclonal antibody blocks malaria transmission and defines a highly conserved neutralizing epitope on gametes.
Coelho, Camila H; Tang, Wai Kwan; Burkhardt, Martin; Galson, Jacob D; Muratova, Olga; Salinas, Nichole D; Alves E Silva, Thiago Luiz; Reiter, Karine; MacDonald, Nicholas J; Nguyen, Vu; Herrera, Raul; Shimp, Richard; Narum, David L; Byrne-Steele, Miranda; Pan, Wenjing; Hou, Xiaohong; Brown, Brittany; Eisenhower, Mary; Han, Jian; Jenkins, Bethany J; Doritchamou, Justin Y A; Smelkinson, Margery G; Vega-Rodríguez, Joel; Trück, Johannes; Taylor, Justin J; Sagara, Issaka; Healy, Sara A; Renn, Jonathan P; Tolia, Niraj H; Duffy, Patrick E.
Affiliation
  • Coelho CH; Pathogenesis and Immunity Section, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Tang WK; Host-Pathogen Interactions and Structural Vaccinology Section, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Burkhardt M; Vaccine Development Unit, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Galson JD; Division of Immunology and Children's Research Center, University Children's Hospital Zurich, University of Zurich (UZH), Zurich, Switzerland.
  • Muratova O; Alchemab Therapeutics Ltd, 55-56 Russell Square, London, UK.
  • Salinas ND; Vaccine Development Unit, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Alves E Silva TL; Host-Pathogen Interactions and Structural Vaccinology Section, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Reiter K; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
  • MacDonald NJ; Vaccine Development Unit, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Nguyen V; Vaccine Development Unit, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Herrera R; Vaccine Development Unit, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Shimp R; Vaccine Development Unit, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Narum DL; Vaccine Development Unit, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Byrne-Steele M; Vaccine Development Unit, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Pan W; iRepertoire Inc., Huntsville, AL, USA.
  • Hou X; iRepertoire Inc., Huntsville, AL, USA.
  • Brown B; iRepertoire Inc., Huntsville, AL, USA.
  • Eisenhower M; iRepertoire Inc., Huntsville, AL, USA.
  • Han J; iRepertoire Inc., Huntsville, AL, USA.
  • Jenkins BJ; iRepertoire Inc., Huntsville, AL, USA.
  • Doritchamou JYA; Pathogenesis and Immunity Section, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Smelkinson MG; Pathogenesis and Immunity Section, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Vega-Rodríguez J; Biological Imaging Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Trück J; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
  • Taylor JJ; Division of Immunology and Children's Research Center, University Children's Hospital Zurich, University of Zurich (UZH), Zurich, Switzerland.
  • Sagara I; Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Healy SA; Malaria Research and Training Center, University of Sciences, Techniques, and Technology, Bamako, Mali.
  • Renn JP; Vaccine Development Unit, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Tolia NH; Vaccine Development Unit, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Duffy PE; Host-Pathogen Interactions and Structural Vaccinology Section, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. niraj.tolia@nih.gov.
Nat Commun ; 12(1): 1750, 2021 03 19.
Article in En | MEDLINE | ID: mdl-33741942
ABSTRACT
Malaria elimination requires tools that interrupt parasite transmission. Here, we characterize B cell receptor responses among Malian adults vaccinated against the first domain of the cysteine-rich 230 kDa gamete surface protein Pfs230, a key protein in sexual stage development of P. falciparum parasites. Among nine Pfs230 human monoclonal antibodies (mAbs) that we generated, one potently blocks transmission to mosquitoes in a complement-dependent manner and reacts to the gamete surface; the other eight show only low or no blocking activity. The structure of the transmission-blocking mAb in complex with vaccine antigen reveals a large discontinuous conformational epitope, specific to domain 1 of Pfs230 and comprising six structural elements in the protein. The epitope is conserved, suggesting the transmission-blocking mAb is broadly functional. This study provides a rational basis to improve malaria vaccines and develop therapeutic antibodies for malaria elimination.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Plasmodium falciparum / Antibodies, Protozoan / Malaria, Falciparum / Germ Cells / Antibodies, Monoclonal / Epitopes Limits: Adult / Animals / Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2021 Document type: Article Affiliation country:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Plasmodium falciparum / Antibodies, Protozoan / Malaria, Falciparum / Germ Cells / Antibodies, Monoclonal / Epitopes Limits: Adult / Animals / Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2021 Document type: Article Affiliation country: