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A human antibody epitope map of Pfs230D1 derived from analysis of individuals vaccinated with a malaria transmission-blocking vaccine.
Tang, Wai Kwan; Coelho, Camila H; Miura, Kazutoyo; Nguemwo Tentokam, Bergeline C; Salinas, Nichole D; Narum, David L; Healy, Sara A; Sagara, Issaka; Long, Carole A; Duffy, Patrick E; Tolia, Niraj H.
Afiliación
  • 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.
  • 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.
  • Miura K; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
  • Nguemwo Tentokam BC; Pathogenesis and Immunity Section, 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.
  • 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.
  • 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.
  • Sagara I; Malaria Research and Training Center, University of Sciences, Techniques, and Technology, Bamako, Mali.
  • Long CA; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
  • 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; Vaccine Development Unit, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and
  • 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. Electronic address: niraj.tolia@nih.gov.
Immunity ; 56(2): 433-443.e5, 2023 02 14.
Article en En | MEDLINE | ID: mdl-36792576
Pfs230 domain 1 (Pfs230D1) is an advanced malaria transmission-blocking vaccine antigen demonstrating high functional activity in clinical trials. However, the structural and functional correlates of transmission-blocking activity are not defined. Here, we characterized a panel of human monoclonal antibodies (hmAbs) elicited in vaccinees immunized with Pfs230D1. These hmAbs exhibited diverse transmission-reducing activity, yet all bound to Pfs230D1 with nanomolar affinity. We compiled epitope-binning data for seventeen hmAbs and structures of nine hmAbs complexes to construct a high-resolution epitope map and revealed that potent transmission-reducing hmAbs bound to one face of Pfs230D1, while non-potent hmAbs bound to the opposing side. The structure of Pfs230D1D2 revealed that non-potent transmission-reducing epitopes were occluded by the second domain. The hmAb epitope map delineated binary hmAb combinations that synergized for extremely high-potency, transmission-reducing activity. This work provides a high-resolution guide for structure-based design of enhanced immunogens and informs diagnostics that measure the transmission-reducing response.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Vacunas contra la Malaria Límite: Humans Idioma: En Revista: Immunity Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Vacunas contra la Malaria Límite: Humans Idioma: En Revista: Immunity Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos