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Record W4382516068 · doi:10.1101/2023.06.26.23291885

Targeting hepatitis B vaccine escape using immunogenetics in Bangladeshi infants

2023· preprint· en· W4382516068 on OpenAlexafffund
Guillaume Butler‐Laporte, Kathryn Auckland, Zannatun Noor, Mamun Kabir, Masud Alam, Tommy Carstensen, Genevieve L. Wojcik, Amanda Y. Chong, Cristina Pomilla, Janelle A. Noble, Shana L. McDevitt, Gaby Smits, Susan Wareing, Fiona van der Klis, Katie Jeffery, Beth D. Kirkpatrick, Sodiomon B. Sirima, Shabir A. Madhi, Alison M. Elliott, J. Brent Richards, Adrian V. S. Hill, Priya Duggal, Manjinder S. Sandhu, Rashidul Haque, William A. Petri, Alexander J. Mentzer

Bibliographic record

VenuemedRxiv · 2023
Typepreprint
Languageen
FieldMedicine
TopicHepatitis B Virus Studies
Canadian institutionsMcGill UniversityJewish General HospitalMcGill University Health Centre
FundersMedical Research CouncilFonds de Recherche du Québec - SantéNational Institute for Health and Care ResearchJewish General HospitalPublic Health AgencyCanadian Institutes of Health ResearchNational Institutes of HealthPublic Health Agency of CanadaCancer Research UKBiomedical Research CouncilRoyal College of Physicians and Surgeons of CanadaWellcome TrustEuropean CommissionBill and Melinda Gates Foundation
KeywordsImmunogenicityVirologyHepatitis B virusEpitopeAntigenBiologyHuman leukocyte antigenImmunologyImmunogeneticsAntibodyAntibody responseHepatitis BVirusMedicine

Abstract

fetched live from OpenAlex

Abstract Hepatitis B virus (HBV) vaccine escape mutants (VEM) are increasingly described, threatening progress in control of this virus worldwide. Here we studied the relationship between host genetic variation, vaccine immunogenicity and viral sequences implicating VEM emergence. In a cohort of 1,096 Bangladeshi children, we identified human leukocyte antigen (HLA) variants associated with response vaccine antigens. Using an HLA imputation panel with 9,448 south Asian individuals DPB1*04:01 was associated with higher HBV antibody responses (p=4.5×10 −30 ). The underlying mechanism is a result of higher affinity binding of HBV surface antigen epitopes to DPB1*04:01 dimers. This is likely a result of evolutionary pressure at the HBV surface antigen ‘a-determinant’ segment incurring VEM specific to HBV. Prioritizing pre-S isoform HBV vaccines may tackle the rise of HBV vaccine evasion. One-Sentence Summary Host genetics underlying hepatitis B vaccine response in Bangladeshi infants identifies mechanisms of viral vaccine escape, and how to prevent it.

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)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.015

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
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)0.0040.001

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 head0.053
GPT teacher head0.317
Teacher spread0.265 · 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 designObservational
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

Citations5
Published2023
Admission routes2
Has abstractyes

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