气候变化领域集成服务门户(CCPortal): Modular complement assemblies for mitigating inflammatory conditions

CCPortal

DOI	10.1073/pnas.2018627118
	Modular complement assemblies for mitigating inflammatory conditions
	Hainline K.M.; Shores L.S.; Votaw N.L.; Bernstein Z.J.; Kelly S.H.; Fries C.N.; Madhira M.S.; Gilroy C.A.; Chilkoti A.; Collier J.H.
发表日期	2021
ISSN	00278424
卷号	118 期号:15
英文摘要	Complement protein C3dg, a key linkage between innate and adaptive immunity, is capable of stimulating both humoral and cell-mediated immune responses, leading to considerable interest in its use as a molecular adjuvant. However, the potential of C3dg as an adjuvant is limited without ways of controllably assembling multiple copies of it into vaccine platforms. Here, we report a strategy to assemble C3dg into supramolecular nanofibers with excellent compositional control, using β-tail fusion tags. These assemblies were investigated as therapeutic active immunotherapies, which may offer advantages over existing biologics, particularly toward chronic inflammatory diseases. Supramolecular assemblies based on the Q11 peptide system containing β-tail-tagged C3dg, B cell epitopes from TNF, and the universal T cell epitope PADRE raised strong antibody responses against both TNF and C3dg, and prophylactic immunization with these materials significantly improved protection in a lethal TNF-mediated inflammation model. Additionally, in a murine model of psoriasis induced by imiquimod, the C3dgadjuvanted nanofiber vaccine performed as well as anti-TNF monoclonal antibodies. Nanofibers containing only β-tail-C3dg and lacking the TNF B cell epitope also showed improvements in both models, suggesting that supramolecular C3dg, by itself, played an important therapeutic role. We observed that immunization with β-tail-C3dg caused the expansion of an autoreactive C3dg-specific T cell population, which may act to dampen the immune response, preventing excessive inflammation. These findings indicate that molecular assemblies displaying C3dg warrant further development as active immunotherapies. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Active immunotherapy; Immune engineering; Immunoengineering; Self-assembly; Vaccine
语种	英语
scopus关键词	alanylcysteinyl glutaminylglutaminyllysylphenylalanylglutaminylphenylalanylglutaminylphenylalanylglutamylglutaminylglutaminyl amide; antipsoriasis agent; complement component C3; complement component C5a; epitope; interleukin 10; monoclonal antibody; nanofiber; tumor necrosis factor; unclassified drug; animal cell; animal tissue; antibody response; Article; B lymphocyte; B lymphocyte activation; CD4+ T lymphocyte; cell population; controlled study; enzyme linked immunosorbent assay; enzyme linked immunospot assay; female; helper cell; imiquimod-induced psoriasis; immune response; immunization; immunotherapy; in vitro study; in vivo study; inflammation; molecular cloning; mouse; nonhuman; priority journal; protein assembly; protein expression; protein purification; transmission electron microscopy
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179884
作者单位	Biomedical Engineering Department, Duke University, Durham, NC 27708, United States
推荐引用方式 GB/T 7714	Hainline K.M.,Shores L.S.,Votaw N.L.,et al. Modular complement assemblies for mitigating inflammatory conditions[J],2021,118(15).
APA	Hainline K.M..,Shores L.S..,Votaw N.L..,Bernstein Z.J..,Kelly S.H..,...&Collier J.H..(2021).Modular complement assemblies for mitigating inflammatory conditions.Proceedings of the National Academy of Sciences of the United States of America,118(15).
MLA	Hainline K.M.,et al."Modular complement assemblies for mitigating inflammatory conditions".Proceedings of the National Academy of Sciences of the United States of America 118.15(2021).