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Record W4221095080 · doi:10.1016/j.celrep.2022.110514

mRNA-encoded HIV-1 Env trimer ferritin nanoparticles induce monoclonal antibodies that neutralize heterologous HIV-1 isolates in mice

2022· article· en· W4221095080 on OpenAlexaff
Zekun Mu, Kevin Wiehe, Kevin O. Saunders, Rory Henderson, Derek W. Cain, Robert Parks, Diana Martik, Katayoun Mansouri, Robert J. Edwards, Amanda Newman, Xiaozhi Lu, Shi-Mao Xia, Amanda Eaton, Mattia Bonsignori, David C. Montefiori, Qi Han, Sravani Venkatayogi, Tyler Evangelous, Yunfei Wang, Wes Rountree, Bette Korber, Kshitij Wagh, Ying K. Tam, Christopher Barbosa, S. Munir Alam, Wilton B. Williams, Ming Tian, Frederick W. Alt, Norbert Pardi, Drew Weissman, Barton F. Haynes

Bibliographic record

VenueCell Reports · 2022
Typearticle
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsAcuitas Therapeutics (Canada)
FundersNational Institute of Allergy and Infectious Diseases
KeywordsGp41HeterologousVirologyMonoclonal antibodyAntibodyTrimerBiologyVirusAntigenChemistryCell biologyMolecular biologyEpitopeGeneGenetics

Abstract

fetched live from OpenAlex

The success of nucleoside-modified mRNAs in lipid nanoparticles (mRNA-LNP) as COVID-19 vaccines heralded a new era of vaccine development. For HIV-1, multivalent envelope (Env) trimer protein nanoparticles are superior immunogens compared with trimers alone for priming of broadly neutralizing antibody (bnAb) B cell lineages. The successful expression of complex multivalent nanoparticle immunogens with mRNAs has not been demonstrated. Here, we show that mRNAs can encode antigenic Env trimers on ferritin nanoparticles that initiate bnAb precursor B cell expansion and induce serum autologous tier 2 neutralizing activity in bnAb precursor V H + V L knock-in mice. Next-generation sequencing demonstrates acquisition of critical mutations, and monoclonal antibodies that neutralize heterologous HIV-1 isolates are isolated. Thus, mRNA-LNP can encode complex immunogens and may be of use in design of germline-targeting and sequential boosting immunogens for HIV-1 vaccine development.

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)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesInsufficient payload (model declined to judge)
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 score0.142
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

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 integrity0.0000.001
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 head0.024
GPT teacher head0.255
Teacher spread0.231 · 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.

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

Citations80
Published2022
Admission routes1
Has abstractyes

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