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In vivo characterization of the physicochemical properties of polymer-linked TLR agonists that enhance vaccine immunogenicity
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SYSNO ASEP 0450872 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název In vivo characterization of the physicochemical properties of polymer-linked TLR agonists that enhance vaccine immunogenicity Tvůrce(i) Lynn, G. M. (US)
Laga, Richard (UMCH-V) RID, ORCID
Darrah, P. A. (US)
Ishizuka, A. S. (US)
Balaci, A. J. (US)
Dulcey, A. E. (US)
Pechar, Michal (UMCH-V) RID, ORCID
Pola, Robert (UMCH-V) RID, ORCID
Gerner, M. Y. (US)
Yamamoto, A. (US)
Buechler, C. R. (US)
Quinn, K. M. (US)
Smelkinson, M. G. (US)
Vanek, O. (CZ)
Cawood, R. (GB)
Hills, T. (GB)
Vasalatiy, O. (US)
Kastenmüller, K. (US)
Francica, J. R. (US)
Stutts, L. (US)
Tom, J. K. (US)
Ah Ryu, K. (US)
Esser-Kahn, A. P. (US)
Etrych, Tomáš (UMCH-V) RID, ORCID
Fisher, K. D. (GB)
Seymour, L. W. (GB)
Seder, R. A. (US)Zdroj.dok. Nature Biotechnology. - : Nature Publishing Group - ISSN 1087-0156
Roč. 33, č. 11 (2015), s. 1201-1210Poč.str. 10 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova adjuvants ; biomedical engineering ; drug delivery Vědní obor RIV CE - Biochemie CEP EE2.3.30.0029 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Institucionální podpora UMCH-V - RVO:61389013 UT WOS 000364916000028 EID SCOPUS 84946572121 DOI 10.1038/nbt.3371 Anotace The efficacy of vaccine adjuvants such as Toll-like receptor agonists (TLRa) can be improved through formulation and delivery approaches. Here, we attached small molecule TLR-7/8a to polymer scaffolds (polymer–TLR-7/8a) and evaluated how different physicochemical properties of the TLR-7/8a and polymer carrier influenced the location, magnitude and duration of innate immune activation in vivo. Particle formation by polymer–TLR-7/8a was the most important factor for restricting adjuvant distribution and prolonging activity in draining lymph nodes. The improved pharmacokinetic profile by particulate polymer–TLR-7/8a was also associated with reduced morbidity and enhanced vaccine immunogenicity for inducing antibodies and T cell immunity. We extended these findings to the development of a modular approach in which protein antigens are site-specifically linked to temperature-responsive polymer–TLR-7/8a adjuvants that self-assemble into immunogenic particles at physiologic temperatures in vivo. Our findings provide a chemical and structural basis for optimizing adjuvant design to elicit broad-based antibody and T cell responses with protein antigens. Pracoviště Ústav makromolekulární chemie Kontakt Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358 Rok sběru 2016
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