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dc.contributor.authorTan, H-X
dc.contributor.authorJegaskanda, S
dc.contributor.authorJuno, JA
dc.contributor.authorEsterbauer, R
dc.contributor.authorWong, J
dc.contributor.authorKelly, HG
dc.contributor.authorLiu, Y
dc.contributor.authorTilmanis, D
dc.contributor.authorHurt, AC
dc.contributor.authorYewdell, JW
dc.contributor.authorKent, SJ
dc.contributor.authorWheatley, AK
dc.date.accessioned2020-12-09T23:44:18Z
dc.date.available2020-12-09T23:44:18Z
dc.date.issued2019-02-01
dc.identifierpii: 123366
dc.identifier.citationTan, H. -X., Jegaskanda, S., Juno, J. A., Esterbauer, R., Wong, J., Kelly, H. G., Liu, Y., Tilmanis, D., Hurt, A. C., Yewdell, J. W., Kent, S. J. & Wheatley, A. K. (2019). Subdominance and poor intrinsic immunogenicity limit humoral immunity targeting influenza HA stem. JOURNAL OF CLINICAL INVESTIGATION, 129 (2), pp.850-862. https://doi.org/10.1172/JCI123366.
dc.identifier.issn0021-9738
dc.identifier.urihttp://hdl.handle.net/11343/253311
dc.description.abstractBoth natural influenza infection and current seasonal influenza vaccines primarily induce neutralizing antibody responses against highly diverse epitopes within the "head" of the viral hemagglutinin (HA) protein. There is increasing interest in redirecting immunity toward the more conserved HA stem or stalk as a means of broadening protective antibody responses. Here we examined HA stem-specific B cell and T follicular helper (Tfh) cell responses in the context of influenza infection and immunization in mouse and monkey models. We found that during infection, the stem domain was immunologically subdominant to the head in terms of serum antibody production and antigen-specific B and Tfh cell responses. Similarly, we found that HA stem immunogens were poorly immunogenic compared with the full-length HA with abolished sialic acid binding activity, with limiting Tfh cell elicitation a potential constraint to the induction or boosting of anti-stem immunity by vaccination. Finally, we confirm that currently licensed seasonal influenza vaccines can boost preexisting memory responses against the HA stem in humans. An increased understanding of the immune dynamics surrounding the HA stem is essential to inform the design of next-generation influenza vaccines for broad and durable protection.
dc.languageEnglish
dc.publisherAMER SOC CLINICAL INVESTIGATION INC
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleSubdominance and poor intrinsic immunogenicity limit humoral immunity targeting influenza HA stem
dc.typeJournal Article
dc.identifier.doi10.1172/JCI123366
melbourne.affiliation.departmentMicrobiology and Immunology
melbourne.affiliation.departmentMelbourne School of Population and Global Health
melbourne.affiliation.department
melbourne.affiliation.departmentDoherty Institute
melbourne.source.titleJournal of Clinical Investigation
melbourne.source.volume129
melbourne.source.issue2
melbourne.source.pages850-862
melbourne.identifier.nhmrc1129099
dc.rights.licenseCC BY
melbourne.elementsid1360386
melbourne.contributor.authorJuno, Jennifer
melbourne.contributor.authorWheatley, Adam
melbourne.contributor.authorJegaskanda, Sinthujan
melbourne.contributor.authorHurt, Aeron
melbourne.contributor.authorEsterbauer, Robyn
melbourne.contributor.authorTan, Hyon Xhi
melbourne.contributor.authorWong, Julius
melbourne.contributor.authorKelly, Hannah
melbourne.contributor.authorLiu, Yi
melbourne.contributor.authorKent, Stephen
melbourne.contributor.authorTilmanis, Danielle
melbourne.contributor.authorKelly, Hannah
dc.identifier.eissn1558-8238
melbourne.identifier.fundernameidNHMRC, 1129099
melbourne.accessrightsOpen Access


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