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Record W4220759987 · doi:10.1101/2022.03.23.485469

CD4 binding-site antibodies induced by a subtype B HIV-1 envelope trimer

2022· preprint· en· W4220759987 on OpenAlexaff
Anna Schorcht, Tom L.G.M. van den Kerkhof, Jon Torres, Edith E. Schermer, Celia C. LaBranche, Ilja Bontjer, Mitch Brinkkemper, Naveed Gulzar, Alvin X. Han, Judith A. Burger, Gabriel Ozorowski, Jamie K. Scott, Hanneke Schuitemaker, David C. Montefiori, Marit J. van Gils, Andrew B. Ward, Rogier W. Sanders

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2022
Typepreprint
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsSimon Fraser University
FundersNederlandse Organisatie voor Wetenschappelijk OnderzoekRijksinstituut voor Volksgezondheid en MilieuBill and Melinda Gates FoundationEuropean CommissionAmsterdam University Medical CentersamfAR, The Foundation for AIDS ResearchNational Institutes of HealthUniversiteit van AmsterdamInternational AIDS Vaccine Initiative
KeywordsTrimerNeutralizationHeterologousAntibodyVirologyPolyclonal antibodiesEpitopeHIV vaccineAvidityGlycoproteinNeutralizing antibodyBinding siteBiologyImmunogenChemistryImmunologyMolecular biologyMonoclonal antibodyVaccine trialBiochemistry

Abstract

fetched live from OpenAlex

Abstract In the last decade considerable advances have been made towards the design of HIV-1 vaccines that induce neutralizing antibodies (NAbs). Despite the progress, no vaccine is able to consistently elicited broadly neutralizing antibodies (bNAbs). Here we present a case study of a rabbit that was immunized with a subtype B native like envelope glycoprotein (Env) trimer, AMC016 SOSIP.v4.2, with a dense and intact glycan shield, followed by a trivalent combination of subtype B trimers. After the priming phase serum from this animal neutralized several heterologous subtype B neutralization resistant (tier 2) viruses. Subsequent immunization with the trivalent combination of subtype B trimers further increased the breadth and potency of the NAb response. EM based polyclonal epitope mapping revealed that a cross reactive CD4 binding-site (CD4bs) antibody response, that was present after priming with the monovalent trimer and boosting with the trivalent combination, was most likely responsible for the broad neutralization. While anecdotal, this study provides proof-of-concept that native-like Env trimers are capable of inducing CD4bs-directed bNAb responses and should guide efforts to improve the consistency with which such responses are generated.

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 score0.005

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)0.0020.000

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 head0.019
GPT teacher head0.247
Teacher spread0.228 · 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

Citations2
Published2022
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicHIV Research and Treatment→French-language works237,207→