Evidence map›Paper›PMID 41762522›Full record

ArticleEBioMedicine2026

Immunodominance is a poor predictor of vaccine-induced T follicular helper cell quality.

Ming Z M Zheng, Hyon-Xhi Tan, Kathleen M Wragg, Lydia Murdiyarso, Devaki Pilapitiya, Andrew Kelly, Robyn Esterbauer, Christopher A Gonelli, Adam K Wheatley, Jennifer A Juno

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In one paragraph

Article in EBioMedicine, 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

10 authors.

Ming Z M ZhengDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia.
Hyon-Xhi TanDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia.
Kathleen M WraggDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia.
Lydia MurdiyarsoDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia.
Devaki PilapitiyaDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia.
Andrew KellyDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia.
Robyn EsterbauerDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia.
Christopher A GonelliDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia.
Adam K WheatleyDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia. Electronic address: a.wheatley@unimelb.edu.au.
Jennifer A JunoDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia. Electronic address: jennifer.juno@unimelb.edu.au.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRational engineering of vaccine immunogens to focus B cell responses on potently neutralising epitopes is a promising approach to improve the potency, breadth and durability of viral vaccines. Such strategies, however, can compromise vaccine immunogenicity through the unintended exclusion of CD4+ T cell epitopes, which are critical for the development of T follicular helper (TFH) cells and to support high affinity antibody production.

methodsUsing a prototypic influenza haemagglutinin (HA) stem immunogen lacking effective CD4+ T cell help in C57BL/6 mice, we interrogated the minimal requirements for T cell help needed to drive serological responses to vaccination.

findingsWe find that priming of naïve CD4+ T cells is markedly efficient, however the immunodominance of a given CD4+ T cell epitope is not predictive of the propensity to provide high quality help to antigen-specific B cells. In the context of soluble antigens, provision of a single MHC class II epitope is sufficient to drive robust germinal centre responses and serum IgG titres. However not all CD4+ epitopes provide equivalent levels of B cell help, despite priming comparable numbers of antigen-specific CD4+ T cells. Finally, we show multimerizing and arraying antigens on nanoparticle scaffolds unlocks highly subdominant, near-undetectable CD4+ T cell helper responses to support a T-dependent antibody response.

interpretationOur findings emphasise the importance of CD4+ T cell help for programming robust and durable humoural immunity, and provide crucial insights to guide the rational incorporation of favourable T cell epitopes into vaccines.

fundingThe study was funded by the NHMRC.

Indexed as

Immunodominant EpitopesInfluenza VaccinesT Follicular Helper CellsT-Lymphocytes, Helper-InducerAnimalsB-LymphocytesCD4-Positive T-LymphocytesEpitopes, T-LymphocyteGerminal CenterHemagglutinin Glycoproteins, Influenza VirusMiceMice, Inbred C57BLEpitopes, T-LymphocyteHemagglutinin Glycoproteins, Influenza VirusImmunodominant EpitopesInfluenza VaccinesCD4 T cellGerminal centreImmunodominanceT follicular helper cellVaccine

Identifiers

PMID41762522
PMCPMC12962106

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

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.