{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T23:56:18Z","timestamp":1787874978674,"version":"build-2784847793"},"reference-count":80,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":343,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008717","name":"Sylvia and Charles Viertel Charitable Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008717","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp; Trans Imm"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Immunisation remains the most cost\u2010effective mechanism to combat influenza infection and is widely employed against seasonal influenza viruses. Zoonotic transmission of avian influenza A viruses represents a significant threat to human health given the lack of population\u2010level immunity. Therefore, there is a need to better understand pre\u2010existing cross\u2010reactive human immunity against avian influenza strains, as highlighted by the recent global spread of avian H5Nx clade 2.3.4.4b variants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here, we quantified the frequencies and specificities of B and T\u2009cells recognising avian hemagglutinin (HA) within unexposed adults and characterised the ability of seasonal immunisation to boost cross\u2010reactive immune responses to H5Nx strains, including from clade 2.3.4.4b.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Low but detectable serum antibody titres against H5 and H7 avian influenza HA were observed in donors. The frequency of memory B cells with cross\u2010reactive recognition of H5 and H7 HA was below 0.13% and two\u2010 to five\u2010fold lower than populations of seasonal HA\u2010specific B cells. Boosting of B\u2010cell responses against clade 2.3.4.4b H5Nx HA following seasonal immunisation was sporadic with only three of 19 individuals showing an increased population of probe\u2010positive cells. Cross\u2010reactive B cells generally expressed immunoglobulins drawn from variable heavy chain genes associated with HA stem recognition. CD4\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell responses towards H5 HA were weakly boosted with little increase in circulating T follicular helper cell populations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings highlight the need for avian influenza\u2010specific vaccine products to bolster immunity in human populations. Such vaccines could aid pre\u2010pandemic preparedness by expanding baseline frequencies of avian influenza\u2010specific memory lymphocytes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cti2.70067","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T04:43:31Z","timestamp":1765428211000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Low\u2010level human memory T and B cells recognising avian influenza hemagglutinins are poorly responsive to existing seasonal influenza vaccines"],"prefix":"10.1002","volume":"14","author":[{"given":"Christopher A","family":"Gonelli","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology Peter Doherty Institute for Infection and Immunity, The University of Melbourne  Melbourne VIC 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Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yee\u2010Chen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Peter Doherty Institute for Infection and Immunity, The University of Melbourne  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda Kyaw","family":"Zin","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Peter Doherty Institute for Infection and Immunity, The University of Melbourne  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara SU","family":"Schwab","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Peter Doherty Institute for Infection and Immunity, The University of Melbourne  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aeron C","family":"Hurt","sequence":"additional","affiliation":[{"name":"WHO Collaborating Centre for Reference and Research on Influenza Peter Doherty Institute for Infection and Immunity  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J","family":"Kent","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Peter Doherty Institute for Infection and Immunity, The University of Melbourne  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A","family":"Juno","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Peter Doherty Institute for Infection and Immunity, The University of Melbourne  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam K","family":"Wheatley","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Peter Doherty Institute for Infection and Immunity, The University of Melbourne  Melbourne VIC 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First Edition [PDF on Internet]. Geneva: World Health Organization [updated 24 February 2025;\u2009cited 18 September 2025]. 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