Thermophobic Trehalose Glycopolymers as Smart C-Type Lectin Receptor Vaccine Adjuvants.

Autor: Hendricksen AT; Department of Chemistry, Washington State University, 1470 NE College Ave, Pullman, WA, 99164, USA., Ezzatpour S; Department of Microbiology and Immunology, Cornell University, 618 Tower Road, Ithaca, NY, 14850, USA., Pulukuri AJ; Department of Chemistry, Washington State University, 1470 NE College Ave, Pullman, WA, 99164, USA., Ryan AT; Department of Chemistry, Washington State University, 1470 NE College Ave, Pullman, WA, 99164, USA., Flanagan TJ; Department of Chemistry, Washington State University, 1470 NE College Ave, Pullman, WA, 99164, USA., Frantz W; Department of Chemistry, Washington State University, 1470 NE College Ave, Pullman, WA, 99164, USA., Buchholz DW; Department of Microbiology and Immunology, Cornell University, 618 Tower Road, Ithaca, NY, 14850, USA., Ortega V; Department of Microbiology and Immunology, Cornell University, 618 Tower Road, Ithaca, NY, 14850, USA., Monreal IA; Department of Microbiology and Immunology, Cornell University, 618 Tower Road, Ithaca, NY, 14850, USA., Sahler JM; Department of Microbiology and Immunology, Cornell University, 618 Tower Road, Ithaca, NY, 14850, USA., Nielsen AE; Astante Therapeutics Inc., 120 N Pine Street, Suite 270A, Spokane, WA, 99202, USA., Aguilar HC; Department of Microbiology and Immunology, Cornell University, 618 Tower Road, Ithaca, NY, 14850, USA., Mancini RJ; Department of Chemistry, Washington State University, 1470 NE College Ave, Pullman, WA, 99164, USA.; Department of Chemistry and Biochemistry, Miami University, 651 E. High Street, Oxford, OH, 45056, USA.
Jazyk: angličtina
Zdroj: Advanced healthcare materials [Adv Healthc Mater] 2023 Jul; Vol. 12 (19), pp. e2202918. Date of Electronic Publication: 2023 Apr 25.
DOI: 10.1002/adhm.202202918
Abstrakt: Herein, this work reports the first synthetic vaccine adjuvants that attenuate potency in response to small, 1-2 °C changes in temperature about their lower critical solution temperature (LCST). Adjuvant additives significantly increase vaccine efficacy. However, adjuvants also cause inflammatory side effects, such as pyrexia, which currently limits their use. To address this, a thermophobic vaccine adjuvant engineered to attenuate potency at temperatures correlating to pyrexia is created. Thermophobic adjuvants are synthesized by combining a rationally designed trehalose glycolipid vaccine adjuvant with thermoresponsive poly-N-isoporpylacrylamide (NIPAM) via reversible addition fragmentation chain transfer (RAFT) polymerization. The resulting thermophobic adjuvants exhibit LCSTs near 37 °C, and self-assembled into nanoparticles with temperature-dependent sizes (90-270 nm). Thermophobic adjuvants activate HEK-mMINCLE and other innate immune cell lines as well as primary mouse bone marrow derived dendritic cells (BMDCs) and bone marrow derived macrophages (BMDMs). Inflammatory cytokine production is attenuated under conditions mimicking pyrexia (above the LCST) relative to homeostasis (37 °C) or below the LCST. This thermophobic behavior correlated with decreased adjuvant R g is observed by DLS, as well as glycolipid-NIPAM shielding interactions are observed by NOESY-NMR. In vivo, thermophobic adjuvants enhance efficacy of a whole inactivated influenza A/California/04/2009 virus vaccine, by increasing neutralizing antibody titers and CD4 + /44 + /62L + lung and lymph node central memory T cells, as well as providing better protection from morbidity after viral challenge relative to unadjuvanted control vaccine. Together, these results demonstrate the first adjuvants with potency regulated by temperature. This work envisions that with further investigation, this approach can enhance vaccine efficacy while maintaining safety.
(© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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