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

Ivanochko, Danton; Fabra-García, Amanda; Teelen, Karina; van de Vegte-Bolmer, Marga; van Gemert, Geert-Jan; Newton, Jocelyn; Semesi, Anthony; de Bruijni, Marloes; Bolscher, Judith; Ramjith, Jordache; Szabat, Marta; Vogt, Stefanie; Kraft, Lucas; Duncan, Sherie; Lee, Shwu-Maan; Kamya, Moses R.; Feeney, Margaret E.; Jagannathan, Prasanna; Greenhouse, Bryan; Sauerwein, Robert W.; King, C. Richter; MacGill, Randall S.; Bousema, Teun; Jore, Matthijs M.; Julien, Jean-Philippe

doi:10.1016/j.immuni.2023.01.013

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

Journal Article · Tue Feb 14 00:00:00 EST 2023 · Immunity

DOI:https://doi.org/10.1016/j.immuni.2023.01.013· OSTI ID:2423565

Ivanochko, Danton ^[1]; Fabra-García, Amanda ^[2]; Teelen, Karina ^[2]; van de Vegte-Bolmer, Marga ^[2]; van Gemert, Geert-Jan ^[2]; Newton, Jocelyn ^[1]; Semesi, Anthony ^[1]; de Bruijni, Marloes ^[3]; Bolscher, Judith ^[3]; Ramjith, Jordache ^[2]; Szabat, Marta ^[4]; Vogt, Stefanie ^[4]; Kraft, Lucas ^[4]; Duncan, Sherie ^[4]; Lee, Shwu-Maan ^[5]; Kamya, Moses R. ^[6]; Feeney, Margaret E. ^[7]; Jagannathan, Prasanna ^[8]; Greenhouse, Bryan ^[7]; Sauerwein, Robert W. ^[3] more »

Hospital for Sick Children Research Institute, Toronto, ON (Canada)
Radboud Univ., Nijmegen (Netherlands)
TropIQ Health Sciences, Nijmegen (Netherlands)
AbCellera Biologics Inc., Vancouver, BC (Canada)
PATH Malaria Vaccine Initiative, Washington, DC (United States)
Infectious Disease Research Collaboration, Kampala (Uganda)
Univ. of California, San Francisco, CA (United States)
Stanford Univ., CA (United States)
Hospital for Sick Children Research Institute, Toronto, ON (Canada); Univ. of Toronto, ON (Canada)

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.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: Bill & Melinda Gates Foundation; European Research Council (ERC); National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 2423565

Journal Information:: Immunity, Journal Name: Immunity Journal Issue: 2 Vol. 56; ISSN 1074-7613

Publisher:: Cell PressCopyright Statement

Country of Publication:: United States

Language:: English

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60 APPLIED LIFE SCIENCES
Immunology
Pfs230
Plasmodium falciparum
human monoclonal antibodies
malaria
natural infection
transmission-blocking

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

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