| First Author | Onishi M | Year | 2015 |
| Journal | J Immunol | Volume | 194 |
| Issue | 6 | Pages | 2673-82 |
| PubMed ID | 25681338 | Mgi Jnum | J:274041 |
| Mgi Id | MGI:6295685 | Doi | 10.4049/jimmunol.1402027 |
| Citation | Onishi M, et al. (2015) Hydroxypropyl-beta-cyclodextrin spikes local inflammation that induces Th2 cell and T follicular helper cell responses to the coadministered antigen. J Immunol 194(6):2673-82 |
| abstractText | Cyclodextrins are commonly used as a safe excipient to enhance the solubility and bioavailability of hydrophobic pharmaceutical agents. Their efficacies and mechanisms as drug-delivery systems have been investigated for decades, but their immunological properties have not been examined. In this study, we reprofiled hydroxypropyl-beta-cyclodextrin (HP-beta-CD) as a vaccine adjuvant and found that it acts as a potent and unique adjuvant. HP-beta-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-beta-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-beta-CD-adjuvanted influenza hemagglutinin split vaccine protected against a lethal challenge with a clinically isolated pandemic H1N1 influenza virus, and the adjuvant effect of HP-beta-CD was demonstrated in cynomolgus macaques. Our results suggest that HP-beta-CD acts as a potent MyD88- and TBK1-dependent T follicular helper cell adjuvant and is readily applicable to various vaccines. |
