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Record W4320730854 · 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

2023· article· en· W4320730854 on OpenAlex
Danton Ivanochko, Amanda Fabra-García, Karina Teelen, Marga van de Vegte‐Bolmer, Geert‐Jan van Gemert, Jocelyn C. Newton, Anthony Semesi, Marloes de Bruijni, Judith M. 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

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueImmunity · 2023
Typearticle
Languageen
FieldMedicine
TopicMalaria Research and Control
Canadian institutionsSickKids FoundationUniversity of TorontoAbCellera (Canada)Hospital for Sick Children
FundersCanadian Institutes of Health ResearchNational Institutes of HealthHospital for Sick ChildrenNederlandse Organisatie voor Wetenschappelijk OnderzoekCanadian Institute for Advanced ResearchNational Institute of Allergy and Infectious DiseasesBill and Melinda Gates Foundation
KeywordsBiologyEpitopePlasmodium falciparumMonoclonal antibodyVirologyAntibodyImmunologyMalaria

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.747
Threshold uncertainty score0.934

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.042
GPT teacher head0.302
Teacher spread0.260 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it