Evidence map›Paper›PMID 42286357›Full record

ArticleNature immunology2026

Human vaccine responses regulated by parallel cytokine pathways.

Guangbo Chen, Jing Guo, John Heath, Tyler R Prestwood, Woo Joo Kwon, Ashley R Smith, Tran T Nguyen, Karan R Kathuria, Elsa Sola, AbuBakr Sangare and 20 more

Abstract read
In one paragraph

Article in Nature immunology, 2026. 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. Article
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

30 authors.

Guangbo Chen *Institute for Immunology, Transplantation and Infection (ITI), Stanford University School of Medicine, Palo Alto, CA, USA. guangbo@mcw.edu.ORCID http://orcid.org/0000-0003-2179-1174
Jing Guo *Department of Microbiology and Immunology, Stanford University School of Medicine, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0002-6616-2585
John Heath *Department of Bioengineering, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-5004-2693
Tyler R PrestwoodDepartment of Medicine, Stanford University School of Medicine, Palo Alto, CA, USA.
Woo Joo KwonDepartment of Medicine, Stanford University School of Medicine, Palo Alto, CA, USA.
Ashley R SmithDepartment of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI, USA.ORCID http://orcid.org/0000-0001-5826-682X
Tran T NguyenThe Human Immune Monitoring Center (HIMC), Stanford University School of Medicine, Palo Alto, CA, USA.
Karan R KathuriaInstitute for Immunology, Transplantation and Infection (ITI), Stanford University School of Medicine, Palo Alto, CA, USA.
Elsa SolaInstitute for Immunology, Transplantation and Infection (ITI), Stanford University School of Medicine, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0001-6897-2760
AbuBakr SangareDepartment of Biology, Stanford University, Stanford, CA, USA.
Vamsee MallajosyulaInstitute for Immunology, Transplantation and Infection (ITI), Stanford University School of Medicine, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0002-0658-3652
Ryan Furuichi FongInstitute for Immunology, Transplantation and Infection (ITI), Stanford University School of Medicine, Palo Alto, CA, USA.ORCID http://orcid.org/0009-0008-1320-0892
Azam MohsinInstitute for Immunology, Transplantation and Infection (ITI), Stanford University School of Medicine, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0003-0021-3244
Lei ChenInstitute for Immunology, Transplantation and Infection (ITI), Stanford University School of Medicine, Palo Alto, CA, USA.
Oviya SivaDepartment of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI, USA.
Cindy PadillaDivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA, USA.
Mingdian TanAsian Liver Center, Department of Surgery, Stanford University School of Medicine, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0003-3064-2189
Cornelia L DekkerDepartment of Pediatrics (Infectious Diseases), Stanford University School of Medicine, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0002-3871-918X
Philip GrantInstitute for Immunology, Transplantation and Infection (ITI), Stanford University School of Medicine, Palo Alto, CA, USA.
Ying LuDepartment of Biomedical Data Science, Stanford University School of Medicine, Palo Alto, CA, USA.
Harry B GreenbergDivision of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA, USA.
William H RobinsonDepartment of Medicine, Stanford University School of Medicine, Palo Alto, CA, USA.
Catherine BlishDivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0001-6946-7627
Shai S Shen-OrrRuth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.ORCID http://orcid.org/0000-0002-6991-7736
Ahmad SalehiDonor Network West, San Ramon, CA, USA.ORCID http://orcid.org/0000-0001-8257-3280
Holden T MaeckerInstitute for Immunology, Transplantation and Infection (ITI), Stanford University School of Medicine, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0003-0795-9946
Purvesh KhatriInstitute for Immunology, Transplantation and Infection (ITI), Stanford University School of Medicine, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0002-4143-4708
Paul J UtzDepartment of Medicine, Stanford University School of Medicine, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0003-1181-1565
Yueh-Hsiu ChienHematopoiesis and Immunobiology Program, Versiti Blood Research Institute, Milwaukee, WI, USA. chien@stanford.edu.ORCID http://orcid.org/0000-0002-6014-1230
Mark M DavisInstitute for Immunology, Transplantation and Infection (ITI), Stanford University School of Medicine, Palo Alto, CA, USA. mmdavis@stanford.edu.ORCID http://orcid.org/0000-0001-6868-657X

Funding

Using a tonsil organoid system to probe conditions for the induction of protective antibody and T cell responses to influenza.U19AI057229 · NIAID · STANFORD UNIVERSITY · PI Mark Morris Davis · 2003 to 2026
$88.5M
Stanford Center for Clinical & Translational Education and Research (Spectrum)UL1TR003142 · NCATS · STANFORD UNIVERSITY · PI O'HARA, RUTH M · 2019 to 2023
$45.0M
The effects of immune-age on immune-response and the molecular mechanisms which drive itP01AI153559 · NIAID · STANFORD UNIVERSITY · PI DAVIS, MARK MORRIS · 2021 to 2025
$17.8M
Vaccination and infection: indicators of immunological health and responsivenessU19AI090019 · NIAID · STANFORD UNIVERSITY · PI DAVIS, MARK MORRIS · 2010 to 2015
$17.3M
Systems biological assessment of T cell responses to vaccinationU19AI167903 · NIAID · STANFORD UNIVERSITY · PI BALI PULENDRAN · 2022 to 2026
$13.2M
A BIOBEHAVIORAL RESEARCH TRAINING PROGRAMT32MH019938 · NIMH · STANFORD UNIVERSITY · PI Corey J Keller, RACHEL MANBER · 1994 to 2026
$9.4M
Mechanisms of BNT162b2 Vaccine Immunogenicity in Systemic Lupus Erythematosus or SclerodermaR01AI182319 · NIAID · STANFORD UNIVERSITY · PI PAUL JOSEPH UTZ, Lisa Zaba · 2024 to 2026
$2.2M
Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation) OPP1113682, INV-008378, INV-076306, INV-070250Bill & Melinda Gates Foundation INV-008378Life Sciences Research Foundation (LSRF) NoneMedical College of Wisconsin (MCW) NoneNational Science Foundation (NSF) NSF GRFP GrantNCATS NIH HHS UL1 TR003142NIAID NIH HHS P01 AI153559NIAID NIH HHS R01 AI182319NIAID NIH HHS U19 AI057229NIAID NIH HHS U19 AI090019NIAID NIH HHS U19 AI167903NIMH NIH HHS T32 MH019938U.S. Department of Health & Human Services | National Institutes of Health (NIH) 1UL1TR003142U.S. Department of Health & Human Services | National Institutes of Health (NIH) 2U19AI057229U.S. Department of Health & Human Services | National Institutes of Health (NIH) 5U19AI090019U.S. Department of Health & Human Services | National Institutes of Health (NIH) CCHI 2U19AI057229-21U.S. Department of Health & Human Services | National Institutes of Health (NIH) CCHI U19 2U19AI057229-16U.S. Department of Health & Human Services | National Institutes of Health (NIH) HIPC U19AI167903U.S. Department of Health & Human Services | National Institutes of Health (NIH) P01AI153559U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01 AI182319-02U.S. Department of Health & Human Services | National Institutes of Health (NIH) T32MH019938U.S. Department of Health & Human Services | National Institutes of Health (NIH) U19AI057229U.S. Department of Health & Human Services | National Institutes of Health (NIH) U19AI090019
6 · The paper itself

Abstract

Human vaccine responses vary widely, but the determinants remain incompletely defined. Here we analyzed 66 cytokines across four inactivated influenza vaccine (IIV) cohorts over five seasons (n = 581) and identified baseline serum interleukin (IL)-18 and interferon (IFN)-β as correlates of day 28 antibody responses. To test causality, we evaluated 19 cytokines in human tonsil and spleen organoids and found that type I IFNs, IL-21 and IL-12, but not IL-18 or IFNγ, enhanced antibody production. The addition of IFNβ to IIV recapitulated key features of the live-vaccine cytokine program. IL-12 and IL-21 defined a parallel pathway independent of type I IFNs, with IL-12 inducing IL-21 in humans, unlike in mice. Delivery of IL-21 or IFNβ via mRNA lipid nanoparticles in vivo promoted long-lived plasma cell formation. Together, these findings define parallel pathways that regulate vaccine immunity. Our approach unites high-throughput organoid testing and human cohort studies, establishing a human-centric platform to identify adjuvant candidates.

Indexed as

CytokinesInfluenza, HumanInfluenza VaccinesAnimalsAntibodies, ViralAntibody FormationHumansInterferon-betaMicePalatine TonsilSpleenVaccines, InactivatedAntibodies, ViralCytokinesInfluenza VaccinesInterferon-betaVaccines, Inactivated

Identifiers

PMID42286357
PMCPMC13414556

What OpenQuestion holds

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LicenceCC BY
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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.