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Record W4401929521 · doi:10.1016/j.cell.2024.07.052

Mosaic sarbecovirus nanoparticles elicit cross-reactive responses in pre-vaccinated animals

2024· article· en· W4401929521 on OpenAlexaff
Alexander A. Cohen, Jennifer R. Keeffe, Ariën Schiepers, Sandra Dross, Allison J. Greaney, Annie V. Rorick, Han Gao, Priyanthi N.P. Gnanapragasam, Chengcheng Fan, Anthony P. West, Arlene I. Ramsingh, Jesse H. Erasmus, Janice D. Pata, Hiromi Muramatsu, Norbert Pardi, Paulo J.C. Lin, Scott Baxter, Rita Cruz, Martina Quintanar‐Audelo, Ellis Robb, Cristina Serrano-Amatriain, Leonardo Magneschi, Ian Fotheringham, Deborah H. Fuller, Gabriel D. Victora, Pamela J. Björkman

Bibliographic record

VenueCell · 2024
Typearticle
Languageen
FieldMedicine
TopicSARS-CoV-2 and COVID-19 Research
Canadian institutionsAcuitas Therapeutics (Canada)
FundersMerkin Institute for Translational Research, California Institute of TechnologyCoalition for Epidemic Preparedness InnovationsWellcome TrustUniversity of UtahCalifornia Institute of TechnologyNational Institutes of HealthCase Western Reserve UniversityWellcome LeapNational Institute of Allergy and Infectious DiseasesRockefeller UniversityPfizerBill and Melinda Gates Foundation
KeywordsBiologyAntibodyVirologyCross-reactivityMosaicAntigenVaccinationImmunologyCross reactions

Abstract

fetched live from OpenAlex

Immunization with mosaic-8b (nanoparticles presenting 8 SARS-like betacoronavirus [sarbecovirus] receptor-binding domains [RBDs]) elicits more broadly cross-reactive antibodies than homotypic SARS-CoV-2 RBD-only nanoparticles and protects against sarbecoviruses. To investigate original antigenic sin (OAS) effects on mosaic-8b efficacy, we evaluated the effects of prior COVID-19 vaccinations in non-human primates and mice on anti-sarbecovirus responses elicited by mosaic-8b, admix-8b (8 homotypics), or homotypic SARS-CoV-2 immunizations, finding the greatest cross-reactivity for mosaic-8b. As demonstrated by molecular fate mapping, in which antibodies from specific cohorts of B cells are differentially detected, B cells primed by WA1 spike mRNA-LNP dominated antibody responses after RBD-nanoparticle boosting. While mosaic-8b- and homotypic-nanoparticles boosted cross-reactive antibodies, de novo antibodies were predominantly induced by mosaic-8b, and these were specific for variant RBDs with increased identity to RBDs on mosaic-8b. These results inform OAS mechanisms and support using mosaic-8b to protect COVID-19-vaccinated/infected humans against as-yet-unknown SARS-CoV-2 variants and animal sarbecoviruses with human spillover potential.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.000

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 head0.038
GPT teacher head0.381
Teacher spread0.343 · 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 source (direct Gemma or distilled Codex), 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

Citations43
Published2024
Admission routes1
Has abstractyes

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