Evidence map›Paper›PMID 40808939›Full record

ArticleFrontiers in immunology2025

AS04 drives superior cross-protective antibody response by increased NOTCH signaling of dendritic cells and proliferation of memory B cells.

Valentino D'Onofrio, Ana Carolina Santana, Marthe Pauwels, Gwenn Waerlop, Anthony Willems, Fien De Boever, Martin Müller, Peter Sehr, Tim Waterboer, Isabel Leroux-Roels and 3 more

Abstract read
In one paragraph

Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Valentino D'OnofrioDepartment of Diagnostic Sciences, Ghent University and Ghent University Hospital, Ghent, Belgium.
Ana Carolina SantanaPathology Advanced Translational Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, United States.
Marthe PauwelsPathology Advanced Translational Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, United States.
Gwenn WaerlopDepartment of Diagnostic Sciences, Ghent University and Ghent University Hospital, Ghent, Belgium.
Anthony WillemsDepartment of Diagnostic Sciences, Ghent University and Ghent University Hospital, Ghent, Belgium.
Fien De BoeverDepartment of Diagnostic Sciences, Ghent University and Ghent University Hospital, Ghent, Belgium.
Martin MüllerDivision of Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Peter SehrChemical Biology Core Facility, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
Tim WaterboerDivision of Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Isabel Leroux-RoelsDepartment of Diagnostic Sciences, Ghent University and Ghent University Hospital, Ghent, Belgium.
Ashish A SharmaPathology Advanced Translational Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, United States.
Rafick Pierre SékalyPathology Advanced Translational Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, United States.
Geert Leroux-RoelsDepartment of Diagnostic Sciences, Ghent University and Ghent University Hospital, Ghent, Belgium.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: The Gardasil-4 Methods: To investigate mechanisms of cross-neutralizing potential, six monozygotic twins (12 females aged 9-13 years) were vaccinated with either Cervarix or Gardasil-4 (2 doses, 6 months apart). Serum neutralizing antibody titers against HPV 6,16,18,31,33,45,52, and 58 were assessed pre-vaccination and 7 days post-second dose. Multi-omic single cell RNA and ATAC sequencing of PBMCs was performed at the latter timepoint. Results: Cervarix generated higher cross-neutralizing antibody titers than Gardasil-4. Higher frequencies of dendritic cells and memory B cells were observed. Gene Set Enrichment Analysis (GSEA) indicated enhanced pathways related to NOTCH2 signaling in DCs and cell cycling/RNA translation in B cells, correlating positively with cross-neutralizing antibody titers. Increased chromatin accessability in genes related to NOTCH signaling in cDC1 was also observed. Cervarix-vaccinated subjects showed increased DC-to-memory B signaling, through upregulation of NOTCH ligands. Engagement of NOTCH was associated to BCL2 expression in memory B cells, supporting an anti-apoptotic state. Conclusion: Increased DC signaling, including NOTCH, through AS04 in Cervarix supports cell survival and sustained RNA translation in memory B cells, 7 days post-vaccination. This may enhance adaptive immune cell maturation, providing a mechanism that can lead to improved cross-reactivity.

Indexed as

Cross ProtectionDendritic CellsMemory B CellsPapillomavirus InfectionsReceptors, NotchAdolescentAntibodies, NeutralizingAntibodies, ViralAntibody FormationCell ProliferationChildFemaleHumansPapillomavirus VaccinesReceptor, Notch2Signal TransductionAntibodies, NeutralizingAntibodies, Viralhuman papillomavirus vaccine, L1 type 16, 18Papillomavirus VaccinesReceptor, Notch2Receptors, Notchadjuvantdendritic cellsHPV vaccineimmune responsememory B cell

Identifiers

PMID40808939
PMCPMC12344523

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.