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Here, we investigated if prior immunization with TIV enhanced disease upon A(H1N1)pdm09 infection in mice. We found that A(H1N1)pdm09 infection in TIV-immunized mice did not enhance the disease, as measured by morbidity and mortality. Instead, TIV-immunized mice cleared A(H1N1)pdm09 virus and recovered at an accelerated rate compared to control mice. Prior TIV immunization was associated with potent inflammatory mediators and virus-specific CD8 T cell activation, but efficient immune regulation, partially mediated by IL-10R-signaling, prevented enhanced disease. Furthermore, in contrast to suggested pathological roles, pre-existing non-neutralizing antibodies (NNAbs) were not associated with enhanced virus replication, but rather with promoted antigen presentation through FcR-bearing cells that led to potent activation of virus-specific CD8 T cells. These findings provide new insights into interactions between pre-existing immunity and pandemic viruses.<\/jats:p>","DOI":"10.1038\/srep37341","type":"journal-article","created":{"date-parts":[[2016,11,16]],"date-time":"2016-11-16T10:13:26Z","timestamp":1479291206000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Non-neutralizing antibodies induced by seasonal influenza vaccine prevent, not exacerbate A(H1N1)pdm09 disease"],"prefix":"10.1038","volume":"6","author":[{"given":"Jin Hyang","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian J.","family":"Reber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amrita","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Sica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nedzad","family":"Music","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhu","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Mishina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Stevens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian A.","family":"York","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshy","family":"Jacob","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suryaprakash","family":"Sambhara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,11,16]]},"reference":[{"key":"BFsrep37341_CR1","doi-asserted-by":"crossref","unstructured":"Novel Swine-Origin Influenza, A. 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Infection and death from influenza A H1N1 virus in Mexico: a retrospective analysis. Lancet 374, 2072\u20132079, doi: 10.1016\/S0140-6736(09)61638-X (2009).","journal-title":"Lancet"},{"key":"BFsrep37341_CR10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2807\/ese.14.31.19288-en","volume":"14","author":"H Kelly","year":"2009","unstructured":"Kelly, H. & Grant, K. Interim analysis of pandemic influenza (H1N1) 2009 in Australia: surveillance trends, age of infection and effectiveness of seasonal vaccination. Euro Surveill 14, 1\u20135 (2009).","journal-title":"Euro Surveill"},{"key":"BFsrep37341_CR11","unstructured":"Centers for Disease, C. & Prevention. Effectiveness of 2008-09 trivalent influenza vaccine against 2009 pandemic influenza A (H1N1)-United States, May-June 2009. 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