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Previously we have extensively characterized\u00a0the viral\u2010vectored universal vaccine, Wyeth\/IL\u201015\/5flu, a group 1 hemagglutinin, H5N1\u2010based vaccine using a vaccinia backbone with interleukin (IL)\u201015. The vaccine elicits robust T\u2010cell responses to provide heterosubtypic protection from lethal infection; however, we have also observed short\u2010term morbidity of vaccinated mice with a disparity between the effects of sublethal infection with group 1 and 2 IAV strains. At day 3 of H3N2 (group 2 IAV) infection, there was a heavily skewed T helper type 1 response in vaccinated infected mice with overproduction of cytokines and reduced chemokines, whereas H1N1 (group 1 IAV) infection had increased innate cellular responses. These findings suggest that increased and early immune activation by T\u2010cell activating vaccines may induce mild immunopathology when there is a mismatch between non\u2010neutralizing antibody and cross\u2010reactive memory T\u2010cell responses leading to exuberant cytokine production. Therefore, to avoid overstimulating proinflammatory immune responses upon infection, universal influenza vaccines that elicit strong T\u2010cell immunity will need a robust cross\u2010reactive antibody response.<\/jats:p>","DOI":"10.1111\/imcb.12608","type":"journal-article","created":{"date-parts":[[2022,11,19]],"date-time":"2022-11-19T16:58:58Z","timestamp":1668877138000},"page":"514-524","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Early vaccine\u2010mediated strain\u2010specific cytokine imbalance induces mild immunopathology during influenza infection"],"prefix":"10.1111","volume":"101","author":[{"given":"Maireid B","family":"Bull","sequence":"first","affiliation":[{"name":"Oxford Vaccine Group, Department of Paediatrics University of Oxford  Oxford UK"},{"name":"UK Chinese Academy of Medical Science (CAMS) Oxford Institute University of Oxford  Oxford UK"},{"name":"HKU\u2010Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong City Hong\u00a0Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fionn NL","family":"Ma","sequence":"additional","affiliation":[{"name":"HKU\u2010Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong City Hong\u00a0Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liyanage P","family":"Perera","sequence":"additional","affiliation":[{"name":"Lymphoid Malignancies Branch, Center for Cancer Research National Cancer Institute, National Institutes of Health  Bethesda USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leo LM","family":"Poon","sequence":"additional","affiliation":[{"name":"HKU\u2010Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong City Hong\u00a0Kong"},{"name":"Division of Public Health Laboratory Sciences, School of Public Health, Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong\u00a0Kong City Hong Kong"},{"name":"Centre for Immunology &amp; Infection Hong Kong Science Park  Shatin Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0768-9926","authenticated-orcid":false,"given":"Sophie A","family":"Valkenburg","sequence":"additional","affiliation":[{"name":"HKU\u2010Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong City Hong\u00a0Kong"},{"name":"Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity University of Melbourne  Melbourne VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,12,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3479"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003207"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy103"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abo1232"},{"key":"e_1_2_9_6_1","unstructured":"CDC.Reporting for bird detections across the United States. 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