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Record W2166730438 · doi:10.1126/science.aac4223

HIV-1 neutralizing antibodies induced by native-like envelope trimers

2015· article· en· W2166730438 on OpenAlexfundno aff
Rogier W. Sanders, Marit J. van Gils, Ronald Derking, Devin Sok, Thomas J. Ketas, Judith A. Burger, Gabriel Ozorowski, Albert Cupo, Cassandra A. Simonich, Leslie Goo, Heather Arendt, Helen J. Kim, Jeong Hyun Lee, Pavel Pugach, Melissa Williams, Gargi Debnath, Brian Moldt, Mariëlle J. van Breemen, Gözde Isik, Max Medina-Ramírez, Jaap Willem Back, Wayne C. Koff, Jean‐Philippe Julien, Eva G. Rakasz, Michael S. Seaman, Miklós Guttman, Kelly K. Lee, Per Johan Klasse, Celia C. LaBranche, William R. Schief, Ian A. Wilson, Julie Overbaugh, Dennis R. Burton, Andrew B. Ward, David C. Montefiori, Hansi Dean, John P. Moore

Bibliographic record

VenueScience · 2015
Typearticle
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsnot available
FundersNational Institute of Allergy and Infectious DiseasesCanadian Institutes of Health ResearchU.S. Public Health ServiceNederlandse Organisatie voor Wetenschappelijk OnderzoekInternational AIDS Vaccine InitiativeNational Institute of General Medical SciencesAids FondsMcKnight FoundationNational Cancer InstituteUnited States Agency for International DevelopmentNational Institutes of HealthBill and Melinda Gates Foundation
KeywordsImmunogenEpitopeAntibodyVirologyGlycoproteinBiologyHuman immunodeficiency virus (HIV)Neutralizing antibodyAIDS VaccinesVirusImmunologyGeneticsMonoclonal antibodyVaccine trial

Abstract

fetched live from OpenAlex

Steps in the right direction HIV-1 mutates rapidly, making it difficult to design a vaccine that will protect people against all of the virus' iterations. A potential successful vaccine design might protect by eliciting broadly neutralizing antibodies (bNAbs), which target specific regions on HIV-1's trimeric envelope glycoprotein (Env) (see the Perspective by Mascola). Jardine et al. used mice engineered to express germline-reverted heavy chains of a particular bNAb and immunized them with an Env-based immunogen designed to bind to precursors of that bNAb. Sanders et al. compared rabbits and monkeys immunized with Env trimers that adopt a nativelike conformation. In both cases, immunized animals produced antibodies that shared similarities with bNAbs. Boosting these animals with other immunogens may drive these antibodies to further mutate into the longsought bNAbs. Chen et al. report that retaining the cytoplasmic domain of Env proteins may be important to attract bNAbs. Removing the cytoplasmic domain may distract the immune response and instead generate antibodies that target epitopes on Env that would not lead to protection. Science , this issue p. 139 , 10.1126/science.aac4223 , p. 156 ; see also p. 191

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 score0.003
Threshold uncertainty score0.009

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 integrity0.0000.001
Insufficient payload (model declined to judge)0.0030.001

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 head0.055
GPT teacher head0.324
Teacher spread0.269 · 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

Citations524
Published2015
Admission routes1
Has abstractyes

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