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Record W4414454154 · doi:10.1101/2025.09.19.25336209

Cross-reactive neuraminidase inhibition antibodies against H5N1 by consecutive influenza A imprinting cohorts of the past century: population-based serosurvey, British Columbia, Canada

2025· preprint· en· W4414454154 on OpenAlexafffundabout
Danuta M. Skowronski, Charlene Ranadheera, Samantha E Kaweski, Suzana Sabaiduc, Lea Separovic, Johnny Ung, Romina C. Reyes, Bonnie Henry, Arianne Albert, Felicity Clemens, Darwyn Kobasa, Nathalie Bastien

Bibliographic record

VenuemedRxiv · 2025
Typepreprint
Languageen
FieldMedicine
TopicRespiratory viral infections research
Canadian institutionsGovernment of British ColumbiaD-Wave Systems (Canada)Public Health Agency of CanadaBC Centre for Disease Control
FundersPublic Health AgencyPublic Health Agency of Canada
KeywordsNeuraminidaseInfluenza A virus subtype H5N1AntibodyPandemicTiterPopulationYoung adultImmune system

Abstract

fetched live from OpenAlex

Abstract Background Avian influenza of the H5N1 subtype shares substantial relatedness in its neuraminidase (NA) surface protein with human influenza A H1N1 viruses of the past century. Understanding variation in pre-existing anti-N1 antibodies against H5N1 is critical to pandemic risk assessment and preparedness. Methods We used anonymized, residual sera collected equally from ten age groups spanning one to >80 years during an August 2024 cross-sectional serosurvey in British Columbia, Canada. We assessed NA inhibition antibody titres by enzyme-linked lectin assay against H5N1 (N=575), H1N1pdm09 (N=250) and H3N2 (N=205). We compared anti-NA titres by birth (imprinting) cohorts defined in relation to historic N1 and/or N2 exposure opportunities. Results Among participants with median age 32 (IQR: 15-62) years, 404 (70%) had cross-reactive anti-N1 titre >10 against H5N1, with 260 (45%), 182 (32%) and 98 (17%), having titres >40, >80 and >160, respectively. H5N1 titres were consistently lower but strongly associated with H1N1pdm09 (r=0.86; 95%CI:0.82-0.89). Geometric mean titres against H1N1pdm09 and H5N1 peaked among young adults born 1997-2003 (427.9, 100.8), declining to lows among young children born 2015-2023 (20.7, 6.8) and middle-aged adults born 1957-1967 (25.1, 10.7), increasing to similar secondary peak among older adults born pre-1947 (387.3, 81.0). Conclusions A substantial proportion of the population has pre-existing, cross-reactive anti-N1 antibodies against H5N1. We interpret variation by age and imprinting cohorts within a unifying hypothesis, emphasizing the role of historic influenza pandemics in expanding and refining the immune repertoire through heightened attack rates and shifts in immunological hierarchies. Our findings have implications for H5N1 and other zoonotic influenza risk assessment.

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)0.001
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 score0.014
Threshold uncertainty score0.090

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.003
Science and technology studies0.0030.001
Scholarly communication0.0010.000
Open science0.0010.001
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 head0.021
GPT teacher head0.317
Teacher spread0.296 · 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

Citations0
Published2025
Admission routes3
Has abstractyes

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