A human monoclonal antibody blocks malaria transmission and defines a highly conserved neutralizing epitope on gametes.

Autor: 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.; Alchemab Therapeutics Ltd, 55-56 Russell Square, London, UK., Muratova O; Vaccine Development Unit, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Salinas ND; 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., Alves E Silva TL; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Reiter K; Vaccine Development Unit, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 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; iRepertoire Inc., Huntsville, AL, 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; Pathogenesis and Immunity Section, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 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; Biological Imaging Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Vega-Rodríguez J; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Trück J; Division of Immunology and Children's Research Center, University Children's Hospital Zurich, University of Zurich (UZH), Zurich, Switzerland., Taylor JJ; Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Sagara I; Malaria Research and Training Center, University of Sciences, Techniques, and Technology, Bamako, Mali., Healy SA; Vaccine Development Unit, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., 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; 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., Duffy PE; Pathogenesis and Immunity Section, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. patrick.duffy@nih.gov.; Vaccine Development Unit, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. patrick.duffy@nih.gov.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Mar 19; Vol. 12 (1), pp. 1750. Date of Electronic Publication: 2021 Mar 19.
DOI: 10.1038/s41467-021-21955-1
Abstrakt: 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.
Databáze: MEDLINE