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In this study, we reprofiled hydroxypropyl-\u03b2-cyclodextrin (HP-\u03b2-CD) as a vaccine adjuvant and found that it acts as a potent and unique adjuvant. HP-\u03b2-CD triggered the innate immune response at the injection site, was trapped by MARCO+ macrophages, increased Ag uptake by dendritic cells, and facilitated the generation of T follicular helper cells in the draining lymph nodes. It significantly enhanced Ag-specific Th2 and IgG Ab responses as potently as did the conventional adjuvant, aluminum salt (alum), whereas its ability to induce Ag-specific IgE was less than that of alum. At the injection site, HP-\u03b2-CD induced the temporary release of host dsDNA, a damage-associated molecular pattern. DNase-treated mice, MyD88-deficient mice, and TBK1-deficient mice showed significantly reduced Ab responses after immunization with this adjuvant. Finally, we demonstrated that HP-\u03b2-CD\u2013adjuvanted influenza hemagglutinin split vaccine protected against a lethal challenge with a clinically isolated pandemic H1N1 influenza virus, and the adjuvant effect of HP-\u03b2-CD was demonstrated in cynomolgus macaques. Our results suggest that HP-\u03b2-CD acts as a potent MyD88- and TBK1-dependent T follicular helper cell adjuvant and is readily applicable to various vaccines.<\/jats:p>","DOI":"10.4049\/jimmunol.1402027","type":"journal-article","created":{"date-parts":[[2015,2,14]],"date-time":"2015-02-14T03:27:12Z","timestamp":1423884432000},"page":"2673-2682","source":"Crossref","is-referenced-by-count":67,"title":["Hydroxypropyl-\u03b2-Cyclodextrin Spikes Local Inflammation That Induces Th2 Cell and T Follicular Helper Cell Responses to the Coadministered Antigen"],"prefix":"10.1093","volume":"194","author":[{"given":"Motoyasu","family":"Onishi","sequence":"first","affiliation":[{"name":"Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation , Osaka 567-0085 ,","place":["Japan"]},{"name":"Laboratory of Vaccine Science, Immunology Frontier Research Center, World Premier Institute, Osaka University , Osaka 565-0871 ,","place":["Japan"]},{"name":"Infectious Diseases, 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