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Potent transmission-blocking monoclonal antibodies from naturally exposed individuals target a conserved epitope on Plasmodium falciparum Pfs230.

Immunity | 2023

Pfs230 is essential for Plasmodium falciparum transmission to mosquitoes and is the protein targeted by the most advanced malaria-transmission-blocking vaccine candidate. Prior understanding of functional epitopes on Pfs230 is based on two monoclonal antibodies (mAbs) with moderate transmission-reducing activity (TRA), elicited from subunit immunization. Here, we screened the B cell repertoire of two naturally exposed individuals possessing serum TRA and identified five potent mAbs from sixteen Pfs230 domain-1-specific mAbs. Structures of three potent and three low-activity antibodies bound to Pfs230 domain 1 revealed four distinct epitopes. Highly potent mAbs from natural infection recognized a common conformational epitope that is highly conserved across P. falciparum field isolates, while antibodies with negligible TRA derived from natural infection or immunization recognized three distinct sites. Our study provides molecular blueprints describing P. falciparum TRA, informed by contrasting potent and non-functional epitopes elicited by natural exposure and vaccination.

Pubmed ID: 36792575 RIS Download

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Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: K24 AI113002
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI093615
  • Agency: NIAID NIH HHS, United States
    Id: U19 AI089674
  • Agency: NIH HHS, United States
    Id: S10 OD012289

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HEK293-F (tool)

RRID:CVCL_6642

Cell line HEK293-F is a Transformed cell line with a species of origin Homo sapiens (Human)

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HEK293-F (tool)

RRID:CVCL_6642

Cell line HEK293-F is a Transformed cell line with a species of origin Homo sapiens (Human)

View all literature mentions