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Subunit vaccines can avoid potential toxicity associated with traditional whole virion\u2010inactivated and live\u2010attenuated vaccines; however, the immunogenicity of subunit vaccines is often poor. A facile method is here reported to produce lipid nanoparticle subunit vaccines that exhibit high immunogenicity and elicit protection against influenza virus. Influenza hemagglutinin (HA) immunogens are functionalized on the surface of liposomes via stable metal chelation chemistry, using a scalable advanced microfluidic mixing technology (NanoAssemblr). Immunization of mice with HA\u2010liposomes elicits increased serum antibody titers and superior protection against highly pathogenic virus challenge compared with free HA protein. HA\u2010liposomal vaccines display enhanced antigen deposition into germinal centers within the draining lymph nodes, driving increased HA\u2010specific B cell, and follicular helper T cell responses. This work provides mechanistic insights into highly protective HA\u2010liposome vaccines and informs the rational design and rapid production of next generation nanoparticle subunit vaccines.<\/jats:p>","DOI":"10.1002\/adhm.202002142","type":"journal-article","created":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T12:54:33Z","timestamp":1615294473000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Hemagglutinin Functionalized Liposomal Vaccines Enhance Germinal Center and Follicular Helper T Cell Immunity"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5570-8557","authenticated-orcid":false,"given":"Mai N.","family":"Vu","sequence":"first","affiliation":[{"name":"Australian Research Council Centre of Excellence in Convergent Bio\u2010Nano Science and Technology Monash University  Parkville VIC 3052 Australia"},{"name":"Monash Institute of Pharmaceutical Sciences Monash University  Parkville VIC 3052 Australia"},{"name":"Peter Doherty Institute for Infection and Immunity University of Melbourne  Melbourne VIC 3000 Australia"},{"name":"Department of Pharmaceutics Hanoi University of Pharmacy  Hanoi 10000 Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah G.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Australian Research Council Centre of Excellence in Convergent Bio\u2010Nano Science and Technology Monash University  Parkville VIC 3052 Australia"},{"name":"Peter Doherty Institute for Infection and Immunity University of Melbourne  Melbourne VIC 3000 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyon\u2010Xhi","family":"Tan","sequence":"additional","affiliation":[{"name":"Australian Research Council Centre of Excellence in Convergent Bio\u2010Nano Science and Technology Monash University  Parkville VIC 3052 Australia"},{"name":"Peter Doherty Institute for Infection and Immunity University of Melbourne  Melbourne VIC 3000 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer A.","family":"Juno","sequence":"additional","affiliation":[{"name":"Peter Doherty Institute for Infection and Immunity University of Melbourne  Melbourne VIC 3000 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robyn","family":"Esterbauer","sequence":"additional","affiliation":[{"name":"Australian Research Council Centre of Excellence in Convergent Bio\u2010Nano Science and Technology Monash University  Parkville VIC 3052 Australia"},{"name":"Peter Doherty Institute for Infection and Immunity University of Melbourne  Melbourne VIC 3000 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas P.","family":"Davis","sequence":"additional","affiliation":[{"name":"Australian Research Council Centre of Excellence in Convergent Bio\u2010Nano Science and Technology Monash University  Parkville VIC 3052 Australia"},{"name":"Monash Institute of Pharmaceutical Sciences Monash University  Parkville VIC 3052 Australia"},{"name":"Australia Institute of Bioengineering &amp; 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