Potent transmission-blocking monoclonal antibodies from naturally exposed individuals target a conserved epitope on Plasmodium falciparum Pfs230
| Autor: | Danton Ivanochko, Amanda Fabra-García, Karina Teelen, Marga van de Vegte-Bolmer, Geert-Jan van Gemert, Jocelyn Newton, Anthony Semesi, Marloes de Bruijni, Judith Bolscher, Jordache Ramjith, Marta Szabat, Stefanie Vogt, Lucas Kraft, Sherie Duncan, Shwu-Maan Lee, Moses R. Kamya, Margaret E. Feeney, Prasanna Jagannathan, Bryan Greenhouse, Robert W. Sauerwein, C. Richter King, Randall S. MacGill, Teun Bousema, Matthijs M. Jore, Jean-Philippe Julien |
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| Rok vydání: | 2023 |
| Předmět: |
All institutes and research themes of the Radboud University Medical Center
lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] Infectious Diseases Immunology lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] Immunology and Allergy Women's cancers Radboud Institute for Health Sciences [Radboudumc 17] |
| Zdroj: | Immunity, 56, 420-432.e7 Immunity, 56, 2, pp. 420-432.e7 |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2023.01.013 |
| Popis: | Contains fulltext : 291404.pdf (Publisher’s version ) (Open Access) 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. |
| Databáze: | OpenAIRE |
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