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The severity of H5N1 infection in humans, as well as the sporadic nature of H5N1 outbreaks, both geographically and temporally, make generation of an effective vaccine a global public health priority. An effective H5N1 vaccine must ultimately provide protection against viruses from diverse clades. Toll-like receptor (TLR) agonist adjuvant formulations have a demonstrated ability to broaden H5N1 vaccine responses in pre-clinical models. However, many of these agonist molecules have proven difficult to develop clinically. Here, we describe comprehensive adjuvant formulation development of the imidazoquinoline TLR-7\/8 agonist 3M-052, in combination with H5N1 hemagglutinin (HA) based antigens. We find that 3M-052 in multiple formulations protects both mice and ferrets from lethal H5N1 homologous virus challenge. Furthermore, we conclusively demonstrate the ability of 3M-052 adjuvant formulations to broaden responses to H5N1 HA based antigens, and show that this broadening is functional using a heterologous lethal virus challenge in ferrets. Given the extensive clinical use of imidazoquinoline TLR agonists for other indications, these studies identify multiple adjuvant formulations which may be rapidly advanced into clinical trials in an H5N1 vaccine.<\/jats:p>","DOI":"10.1038\/srep46426","type":"journal-article","created":{"date-parts":[[2017,4,21]],"date-time":"2017-04-21T05:49:02Z","timestamp":1492753742000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["A Formulated TLR7\/8 Agonist is a Flexible, Highly Potent and Effective Adjuvant for Pandemic Influenza Vaccines"],"prefix":"10.1038","volume":"7","author":[{"given":"Neal","family":"Van Hoeven","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher B.","family":"Fox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Granger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara","family":"Evers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharvari W.","family":"Joshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghislain I.","family":"Nana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah C.","family":"Evans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rie","family":"Nakajima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip L.","family":"Felgner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Bowen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Marlenee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Airn","family":"Hartwig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan L.","family":"Baldwin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhea N.","family":"Coler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Tomai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Elvecrog","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven G.","family":"Reed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darrick","family":"Carter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,4,21]]},"reference":[{"key":"BFsrep46426_CR1","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.virusres.2013.05.012","volume":"178","author":"Y Guan","year":"2013","unstructured":"Guan, Y. & Smith, G. J. The emergence and diversification of panzootic H5N1 influenza viruses. Virus Res 178, 35\u201343, doi: 10.1016\/j.virusres.2013.05.012 (2013).","journal-title":"Virus Res"},{"key":"BFsrep46426_CR2","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.virusres.2013.05.009","volume":"178","author":"S Sonnberg","year":"2013","unstructured":"Sonnberg, S., Webby, R. J. & Webster, R. G. Natural history of highly pathogenic avian influenza H5N1. Virus Res 178, 63\u201377, doi: 10.1016\/j.virusres.2013.05.009 (2013).","journal-title":"Virus Res"},{"key":"BFsrep46426_CR3","unstructured":"WHO. Cumulative number of confirmed human cases of avian influenza A(H5N1) reported to WHO, http:\/\/www.who.int\/influenza\/human_animal_interface\/H5N1_cumulative_table_archives\/en\/ (2016)."},{"key":"BFsrep46426_CR4","doi-asserted-by":"publisher","first-page":"1534","DOI":"10.1126\/science.1213362","volume":"336","author":"S Herfst","year":"2012","unstructured":"Herfst, S. et al. 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