Evidence map›Paper›PMID 39986275›Full record

ArticleCell stem cell2025

Systems immunology analysis of human immune organoids identifies host-specific correlates of protection to different influenza vaccines.

Zachary W Wagoner, Timothy B Yates, Jenny E Hernandez-Davies, Suhas Sureshchandra, Erika M Joloya, Aarti Jain, Rafael de Assis, Jenna M Kastenschmidt, Andrew M Sorn, Mahina Tabassum Mitul and 7 more

Abstract read
In one paragraph

Article in Cell stem cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed.

  1. Review
  2. A tonsil organoid model reveals Epstein-Barr virus-infected germinal center B cell states during primary infection.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Review
  4. Human Organoids as a Novel Tool for Vaccine Study.Advanced healthcare materials · 2026
    Review
  5. Lymphoid-Tissue-on-Chip Recapitulates Human Antibody Responses In Vitro.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Organoids: physiologically relevantJournal of virology · 2025
    Review
  15. Review
  16. Emerging technologies and current challenges in intratumoral microbiota research.Frontiers in cellular and infection microbiology · 2025
    Review
  17. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Zachary W WagonerDepartment of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA; Institute for Immunology, University of California, Irvine, Irvine, CA, USA; Center for Virus Research, University of California, Irvine, Irvine, CA, USA; Vaccine R&D Center, University of California, Irvine, Irvine, CA, USA.
Timothy B YatesDepartment of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA; Institute for Immunology, University of California, Irvine, Irvine, CA, USA; Center for Virus Research, University of California, Irvine, Irvine, CA, USA; Vaccine R&D Center, University of California, Irvine, Irvine, CA, USA.
Jenny E Hernandez-DaviesDepartment of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA; Institute for Immunology, University of California, Irvine, Irvine, CA, USA; Center for Virus Research, University of California, Irvine, Irvine, CA, USA; Vaccine R&D Center, University of California, Irvine, Irvine, CA, USA.
Suhas SureshchandraDepartment of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA; Institute for Immunology, University of California, Irvine, Irvine, CA, USA; Center for Virus Research, University of California, Irvine, Irvine, CA, USA; Vaccine R&D Center, University of California, Irvine, Irvine, CA, USA.
Erika M JoloyaDepartment of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA; Institute for Immunology, University of California, Irvine, Irvine, CA, USA; Center for Virus Research, University of California, Irvine, Irvine, CA, USA; Vaccine R&D Center, University of California, Irvine, Irvine, CA, USA.
Aarti JainDepartment of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA; Institute for Immunology, University of California, Irvine, Irvine, CA, USA; Vaccine R&D Center, University of California, Irvine, Irvine, CA, USA.
Rafael de AssisDepartment of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA; Institute for Immunology, University of California, Irvine, Irvine, CA, USA; Vaccine R&D Center, University of California, Irvine, Irvine, CA, USA.
Jenna M KastenschmidtDepartment of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA; Institute for Immunology, University of California, Irvine, Irvine, CA, USA; Center for Virus Research, University of California, Irvine, Irvine, CA, USA; Vaccine R&D Center, University of California, Irvine, Irvine, CA, USA.
Andrew M SornDepartment of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA; Institute for Immunology, University of California, Irvine, Irvine, CA, USA; Center for Virus Research, University of California, Irvine, Irvine, CA, USA; Vaccine R&D Center, University of California, Irvine, Irvine, CA, USA.
Mahina Tabassum MitulDepartment of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA; Institute for Immunology, University of California, Irvine, Irvine, CA, USA; Center for Virus Research, University of California, Irvine, Irvine, CA, USA; Vaccine R&D Center, University of California, Irvine, Irvine, CA, USA.
Ian TamburiniDepartment of Biological Chemistry, University of California, Irvine, Irvine, CA, USA; Center for Epigenetics and Metabolism, University of California, Irvine, Irvine, CA, USA.
Gurpreet AhujaDepartment of Pediatric Otolaryngology, Children's Hospital of Orange County, Orange, CA, USA; Department of Otolaryngology-Head and Neck Surgery, University of California, Irvine, Orange, CA, USA.
Qiu ZhongDepartment of Pediatric Otolaryngology, Children's Hospital of Orange County, Orange, CA, USA; Department of Otolaryngology-Head and Neck Surgery, University of California, Irvine, Orange, CA, USA.
Douglas TraskDepartment of Otolaryngology-Head and Neck Surgery, University of California, Irvine, Orange, CA, USA.
Marcus SeldinDepartment of Biological Chemistry, University of California, Irvine, Irvine, CA, USA; Center for Epigenetics and Metabolism, University of California, Irvine, Irvine, CA, USA.
D Huw DaviesDepartment of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA; Institute for Immunology, University of California, Irvine, Irvine, CA, USA; Center for Virus Research, University of California, Irvine, Irvine, CA, USA; Vaccine R&D Center, University of California, Irvine, Irvine, CA, USA.
Lisa E WagarDepartment of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA; Institute for Immunology, University of California, Irvine, Irvine, CA, USA; Center for Virus Research, University of California, Irvine, Irvine, CA, USA; Vaccine R&D Center, University of California, Irvine, Irvine, CA, USA. Electronic address: lwagar@hs.uci.edu.

Funding

Investigating protective adaptive immune responses to influenza antigens using human tonsil organoidsR01AI173023 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI Lisa Wagar · 2023 to 2026
$2.5M
Immunology Research Training GrantT32AI177324 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI Eric Pearlman · 2023 to 2026
$735k
NIAID NIH HHS R01 AI173023NIAID NIH HHS T32 AI177324Wellcome Trust
6 · The paper itself

Abstract

Vaccines are an essential tool to significantly reduce pathogen-related morbidity and mortality. However, our ability to rationally design vaccines and identify correlates of protection remains limited. Here, we employed an immune organoid approach to capture human adaptive immune response diversity to influenza vaccines and systematically identify host and antigen features linked to vaccine response variability. Our investigation identified established and unique immune signatures correlated with neutralizing antibody responses across seven different influenza vaccines and antigens. Unexpectedly, heightened ex vivo tissue frequencies of T helper (Th)1 cells emerged as both a predictor and a correlate of neutralizing antibody responses to inactivated influenza vaccines (IIVs). Secondary analysis of human public data confirmed that elevated Th1 signatures are associated with antibody responses following in vivo vaccination. These findings demonstrate the utility of human in vitro models for identifying in vivo correlates of protection and establish a role for Th1 functions in influenza vaccination.

Indexed as

Influenza, HumanInfluenza VaccinesOrganoidsAntibodies, NeutralizingAntibodies, ViralHumansImmunoinformaticsTh1 CellsVaccinationAntibodies, NeutralizingAntibodies, ViralInfluenza Vaccinesadaptive immunityhumoral immunityimmune organoidslymphoid tissuespredictive modelingsystems immunologyvaccines

Identifiers

PMID39986275
PMCPMC11974613

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Registered trials

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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.