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Record W4414826432 · doi:10.1101/2025.10.03.679932

Mucosal vaccine immunity induced by a new auxotrophic <i>Pseudomonas aeruginosa</i> strain is linked to Th17 and IgA responses

2025· preprint· en· W4414826432 on OpenAlexaff
Youssouf Sérémé, Bérengère Villeret, Ségolène Caboche, Samuel IKEH, Delphine Beury, Florence Maurier, Christophe Desterke, Maëlys Born-Bony, Romé Voulhoux

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGut microbiota and health
Canadian institutionsMcMaster University
FundersCentre National de la Recherche ScientifiqueInstitut National de la Santé et de la Recherche Médicale
KeywordsImmune systemPathogenStrain (injury)ImmunityAttenuated vaccinePhenotypeHumoral immunityMucosal immunology

Abstract

fetched live from OpenAlex

ABSTRACT Pseudomonas aeruginosa ( P.a ) is a Gram-negative opportunistic pathogen that poses a major global health threat, particularly in immunocompromised individuals, patients with cystic fibrosis, and those with burn injuries or ventilator-associated pneumonia. Despite intense efforts, no licensed vaccine is currently available for human use. In this context, live attenuated vaccines (LAVs) represent a promising but underexplored approach, offering the potential to elicit robust, long-lasting, and multifaceted immune responses including that of inducing trained immunity. Here, we sub-cultured Δ LasB PAO1 (a P.a strain that we have shown previously shown to have reduced virulence) in artificial sputum medium (ASM), a culture medium mimicking CF sputum in which bacteria often show auxotrophy. We showed that such a strain (designed here ‘V’ for vaccine) was auxotrophic, less virulent, and had characteristics of ‘CF-like strains’. Crucially, V was able to induce both local (IgA) and systemic humoral responses as well as memory Th17 immune responses, and could, when administered intra-tracheally (but not intra-muscularly), fully protected mice against a lethal PAO1 infection. Overall, the present study demonstrates that our vaccine formulation, in addition to providing an advantageous auxotrophic phenotype adapted to the CF setting, was efficient, when given mucosally, in preferentially inducing secretory IgA and Th17 pathway at mucosal surfaces, a critical barrier that neutralizes pathogens before tissue invasion.

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 score0.001
Threshold uncertainty score0.003

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)0.0010.000

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 head0.014
GPT teacher head0.254
Teacher spread0.240 · 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

Citations0
Published2025
Admission routes1
Has abstractyes

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