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Record W4315619806 · doi:10.1128/mbio.03370-22

A Germline-Targeting Chimpanzee SIV Envelope Glycoprotein Elicits a New Class of V2-Apex Directed Cross-Neutralizing Antibodies

2023· article· en· W4315619806 on OpenAlexafffund
Frédéric Bibollet‐Ruche, Ronnie M. Russell, Wenge Ding, Weimin Liu, Yingying Li, Kshitij Wagh, Daniel Wrapp, Rumi Habib, Ashwin N. Skelly, Ryan S. Roark, Scott Sherrill-Mix, Shuyi Wang, Juliette Rando, Emily Lindemuth, Kendra Cruickshank, Young-Hoon Park, Rachel Baum, John W. Carey, Andrew Connell, Hui Li, Elena E. Giorgi, Ge Song, Shilei Ding, Andrés Finzi, Amanda Newman, Giovanna E. Hernandez, Emily Machiele, Derek W. Cain, Katayoun Mansouri, Mark G. Lewis, David C. Montefiori, Kevin Wiehe, S. Munir Alam, I‐Ting Teng, Peter D. Kwong, Raiees Andrabi, Laurent Verkoczy, Dennis R. Burton, Bette Korber, Kevin O. Saunders, Barton F. Haynes, Robert J. Edwards, George M. Shaw, Beatrice H. Hahn

Bibliographic record

VenuemBio · 2023
Typearticle
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsUniversité de MontréalCentre Hospitalier de l’Université de Montréal
FundersCanadian Institutes of Health ResearchNational Institutes of HealthVaccine Research CenterCenter for AIDS Research, University of WashingtonUniversity of PennsylvaniaNational Institute of Allergy and Infectious DiseasesDivision of Intramural Research, National Institute of Allergy and Infectious Diseases
KeywordsGermlineBiologyApex (geometry)GlycoproteinAntibodyVirologyCell biologyPrimateImmunologyGeneticsGeneNeuroscienceAnatomy

Abstract

fetched live from OpenAlex

An effective HIV-1 vaccination strategy will need to stimulate rare precursor B cells of multiple bNAb lineages and affinity mature them along desired pathways. Here, we searched for V2-apex germ line-targeting Envs among a large set of diverse primate lentiviruses and identified minimally modified versions of one chimpanzee SIV Env that bound several human V2-apex bNAb precursors and stimulated one of these in a V2-apex bNAb precursor-expressing knock-in mouse. We also generated chimeric simian-chimpanzee immunodeficiency viruses and showed that they elicit low-titer V2-directed heterologous plasma breadth in six of seven infected rhesus macaques. Characterization of this antibody response identified a new class of weakly cross-reactive neutralizing antibodies that target the V2-apex, but only in occluded-open Env trimers. The existence of this cryptic epitope, which in some Env backgrounds is immunodominant, needs to be considered in immunogen design.

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 score0.244
Threshold uncertainty score0.998

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 integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.003

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 head0.026
GPT teacher head0.310
Teacher spread0.284 · 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

Citations13
Published2023
Admission routes2
Has abstractyes

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