MétaCan
Menu
Back to cohort
Record W4320730822 · doi:10.1016/j.immuni.2023.01.009

Highly potent, naturally acquired human monoclonal antibodies against Pfs48/45 block Plasmodium falciparum transmission to mosquitoes

2023· article· en· W4320730822 on OpenAlexafffund
Amanda Fabra-García, Sophia Hailemariam, Roos M. de Jong, Kirsten Janssen, Karina Teelen, Marga van de Vegte‐Bolmer, Geert‐Jan van Gemert, Danton Ivanochko, Anthony Semesi, Brandon McLeod, Martijn Vos, Marloes H.C. de Bruijni, Judith M. Bolscher, Marta Szabat, Stefanie Vogt, Lucas Kraft, Sherie Duncan, Moses R. Kamya, Margaret E. Feeney, Prasanna Jagannathan, Bryan Greenhouse, Koen J. Dechering, Robert W. Sauerwein, C. Richter King, Randall S. MacGill, Teun Bousema, Jean‐Philippe Julien, Matthijs M. Jore

Bibliographic record

VenueImmunity · 2023
Typearticle
Languageen
FieldMedicine
TopicMalaria Research and Control
Canadian institutionsSickKids FoundationAbCellera (Canada)Hospital for Sick ChildrenUniversity of Toronto
FundersNational Institute of Allergy and Infectious DiseasesCanadian Institutes of Health ResearchBill and Melinda Gates FoundationOffice of ScienceUniversity of TorontoNational Cancer InstituteNational Institutes of HealthHospital for Sick ChildrenNederlandse Organisatie voor Wetenschappelijk OnderzoekNational Institute of General Medical SciencesCanadian Institute for Advanced ResearchArgonne National LaboratoryU.S. Department of Energy
KeywordsMonoclonal antibodyBiologyPlasmodium falciparumEpitopeVirologyMalariaMalaria vaccineAntibodyParasite hostingTransmission (telecommunications)Immunology

Abstract

fetched live from OpenAlex

Malaria transmission-blocking vaccines (TBVs) aim to induce antibodies that interrupt malaria parasite development in the mosquito, thereby blocking onward transmission, and provide a much-needed tool for malaria control and elimination. The parasite surface protein Pfs48/45 is a leading TBV candidate. Here, we isolated and characterized a panel of 81 human Pfs48/45-specific monoclonal antibodies (mAbs) from donors naturally exposed to Plasmodium parasites. Genetically diverse mAbs against each of the three domains (D1-D3) of Pfs48/45 were identified. The most potent mAbs targeted D1 and D3 and achieved >80% transmission-reducing activity in standard membrane-feeding assays, at 10 and 2 μg/mL, respectively. Co-crystal structures of D3 in complex with four different mAbs delineated two conserved protective epitopes. Altogether, these Pfs48/45-specific human mAbs provide important insight into protective and non-protective epitopes that can further our understanding of transmission and inform the design of refined malaria transmission-blocking vaccine candidates.

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.

How this classification was reachedexpand

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)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.859
Threshold uncertainty score0.968

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

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 head0.028
GPT teacher head0.316
Teacher spread0.288 · 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

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations37
Published2023
Admission routes2
Has abstractyes

Explore more

Same venueImmunitySame topicMalaria Research and ControlFrench-language works237,207