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dc.contributor.authorHill, Danika L
dc.contributor.authorWhyte, Carly E
dc.contributor.authorInnocentin, Silvia
dc.contributor.authorLee, Jia Le
dc.contributor.authorDooley, James
dc.contributor.authorWang, Jiong
dc.contributor.authorJames, Eddie A
dc.contributor.authorLee, James C
dc.contributor.authorKwok, William W
dc.contributor.authorZand, Martin S
dc.contributor.authorListon, Adrian
dc.contributor.authorCarr, Edward J
dc.contributor.authorLinterman, Michelle
dc.date.accessioned2022-01-06T12:54:32Z
dc.date.available2022-01-06T12:54:32Z
dc.date.issued2021-11-02
dc.identifier.issn2050-084X
dc.identifier.otherPMC8562996
dc.identifier.other34726156
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332198
dc.descriptionFunder: National Institute for Health Research (NIHR)
dc.description.abstractAntibody production following vaccination can provide protective immunity to subsequent infection by pathogens such as influenza viruses. However, circumstances where antibody formation is impaired after vaccination, such as in older people, require us to better understand the cellular and molecular mechanisms that underpin successful vaccination in order to improve vaccine design for at-risk groups. Here, by studying the breadth of anti-haemagglutinin (HA) IgG, serum cytokines, and B and T cell responses by flow cytometry before and after influenza vaccination, we show that formation of circulating T follicular helper (cTfh) cells was associated with high-titre antibody responses. Using Major Histocompatability Complex (MHC) class II tetramers, we demonstrate that HA-specific cTfh cells can derive from pre-existing memory CD4+ T cells and have a diverse T cell receptor (TCR) repertoire. In older people, the differentiation of HA-specific cells into cTfh cells was impaired. This age-dependent defect in cTfh cell formation was not due to a contraction of the TCR repertoire, but rather was linked with an increased inflammatory gene signature in cTfh cells. Together, this suggests that strategies that temporarily dampen inflammation at the time of vaccination may be a viable strategy to boost optimal antibody generation upon immunisation of older people.
dc.languageeng
dc.publishereLife Sciences Publications, Ltd
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 2050-084X
dc.sourcenlmid: 101579614
dc.subjectHuman
dc.subjectAntibodies
dc.subjectVaccines
dc.subjectMouse
dc.subjectAgeing
dc.subjectInfluenza
dc.subjectInflammation
dc.subjectimmunology
dc.subjectT Follicular Helper Cells
dc.subjectGerminal Centre
dc.subjectHumans
dc.subjectInfluenza Vaccines
dc.subjectHemagglutinins
dc.subjectVaccination
dc.subjectAntibody Formation
dc.titleImpaired HA-specific T follicular helper cell and antibody responses to influenza vaccination are linked to inflammation in humans.
dc.typeArticle
dc.date.updated2022-01-06T12:54:31Z
prism.publicationNameElife
prism.volume10
dc.identifier.doi10.17863/CAM.79644
dcterms.dateAccepted2021-10-08
rioxxterms.versionofrecord10.7554/eLife.70554
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidHill, Danika L [0000-0001-6284-7061]
dc.contributor.orcidCarr, Edward J [0000-0001-9343-4593]
dc.contributor.orcidLinterman, Michelle [0000-0001-6047-1996]
dc.identifier.eissn2050-084X
pubs.funder-project-idWellcome Trust (105920/Z/14/Z)
cam.issuedOnline2021-11-02


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International