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Record W4302293779 · doi:10.1038/s41467-022-33309-6

DNA-delivered antibody cocktail exhibits improved pharmacokinetics and confers prophylactic protection against SARS-CoV-2

2022· article· en· W4302293779 on OpenAlexafffund
Elizabeth M. Parzych, Jianqiu Du, Ali Ali, Katherine Schultheis, Drew Frase, Trevor R.F. Smith, Jiayan Cui, Neethu Chokkalingam, Nicholas J. Tursi, Viviane M. Andrade, Bryce M. Warner, E. Gary, Yue Li, Jihae Choi, Jillian Eisenhauer, Igor Maricic, Abhijeet J. Kulkarni, Jacqueline D. Chu, Gabrielle Villafana, Kim Rosenthal, Kuishu Ren, Joseph R. Francica, Sarah K. Wootton, Pablo Tebas, Darwyn Kobasa, Kate E. Broderick, Jean Boyer, Mark T. Esser, Jesper Pallesen, Dan W. Kulp, Ami Patel, David B. Weiner

Bibliographic record

VenueNature Communications · 2022
Typearticle
Languageen
FieldMedicine
TopicSARS-CoV-2 and COVID-19 Research
Canadian institutionsUniversity of GuelphUniversity of ManitobaPublic Health Agency of Canada
FundersDefense Advanced Research Projects AgencyNational Cancer InstituteNational Institutes of HealthU.S. Department of Health and Human ServicesPublic Health Agency of CanadaIndiana University BloomingtonPurdue UniversityNational Institute of Allergy and Infectious DiseasesDivision of Intramural Research, National Institute of Allergy and Infectious DiseasesU.S. Department of Defense
KeywordsMonoclonal antibodyIn vivoAntibodyVirologyRecombinant DNACoronavirus disease 2019 (COVID-19)PharmacokineticsPotencySevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)MedicineTiterEx vivo2019-20 coronavirus outbreakAntigenComputational biologyImmunologyBiologyIn vitroPharmacologyInfectious disease (medical specialty)OutbreakDiseaseBiochemistryGenetics

Abstract

fetched live from OpenAlex

Monoclonal antibody therapy has played an important role against SARS-CoV-2. Strategies to deliver functional, antibody-based therapeutics with improved in vivo durability are needed to supplement current efforts and reach underserved populations. Here, we compare recombinant mAbs COV2-2196 and COV2-2130, which compromise clinical cocktail Tixagevimab/Cilgavimab, with optimized nucleic acid-launched forms. Functional profiling of in vivo-expressed, DNA-encoded monoclonal antibodies (DMAbs) demonstrated similar specificity, broad antiviral potency and equivalent protective efficacy in multiple animal challenge models of SARS-CoV-2 prophylaxis compared to protein delivery. In PK studies, DNA-delivery drove significant serum antibody titers that were better maintained compared to protein administration. Furthermore, cryo-EM studies performed on serum-derived DMAbs provide the first high-resolution visualization of in vivo-launched antibodies, revealing new interactions that may promote cooperative binding to trimeric antigen and broad activity against VoC including Omicron lineages. These data support the further study of DMAb technology in the development and delivery of valuable biologics.

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 score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.051
GPT teacher head0.378
Teacher spread0.328 · 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

Citations31
Published2022
Admission routes2
Has abstractyes

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