7uvi
Pfs230 domain 1 bound by RUPA-55 Fab
Structural highlights
FunctionP230_PLAF7 Gametocyte surface protein required for male/female gamete fusion. Also required for male gamete exflagellation and interaction with erythrocytes.[1] Publication Abstract from PubMedPfs230 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. Potent transmission-blocking monoclonal antibodies from naturally exposed individuals target a conserved epitope on Plasmodium falciparum Pfs230.,Ivanochko D, Fabra-Garcia A, Teelen K, van de Vegte-Bolmer M, van Gemert GJ, Newton J, Semesi A, de Bruijni M, Bolscher J, Ramjith J, Szabat M, Vogt S, Kraft L, Duncan S, Lee SM, Kamya MR, Feeney ME, Jagannathan P, Greenhouse B, Sauerwein RW, Richter King C, MacGill RS, Bousema T, Jore MM, Julien JP Immunity. 2023 Feb 14;56(2):420-432.e7. doi: 10.1016/j.immuni.2023.01.013. PMID:36792575[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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