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α-半乳糖神经酰胺(αGalCer)增强蓖麻毒素中毒模型中的疫苗诱导保护作用。

Alpha-galactosylceramide (αGalCer) enhances vaccine-induced protection in a model of ricin intoxication.

机构信息

a Division of Infectious Disease, Wadsworth Center, New York State Department of Health , Albany , NY.

b Department of Microbiology, Immunology, and Molecular Genetics , The University of Texas Health Science Center at San Antonio , San Antonio , TX.

出版信息

Hum Vaccin Immunother. 2018;14(8):2053-2057. doi: 10.1080/21645515.2018.1461299. Epub 2018 May 14.

DOI:10.1080/21645515.2018.1461299
PMID:29617191
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6150012/
Abstract

Alpha-galactosylceramide (αGalCer) is a glycolipid derived from a marine sponge that is a potent activator of both mouse and human invariant natural killer T (iNKT) cells. For that reason, αGalCer is a promising vaccine adjuvant that has been shown to improve both humoral and cellular immunity when co-administered with various vaccines, including candidate vaccines for biodefense. In the current study, we tested the effectiveness of αGalCer as an adjuvant for the clinically-relevant ricin toxin subunit vaccine, RiVax. αGalCer had a potent adjuvant effect, as shown by a rapid onset of anti-ricin IgG titers, accelerated development of serum toxin-neutralizing activity, and enhanced protection from lethal ricin challenge in a mouse model. These results underscore the potential of αGalCer to augment the protective immune response to a vaccine designed to counteract ricin toxin, a fast-acting biothreat agent.

摘要

α-半乳糖神经酰胺(αGalCer)是一种来源于海洋海绵的糖脂,能够激活人和鼠的天然不变自然杀伤 T(iNKT)细胞。因此,αGalCer 是一种很有前途的疫苗佐剂,与各种疫苗联合使用时,可改善体液和细胞免疫,包括用于生物防御的候选疫苗。在本研究中,我们测试了αGalCer 作为临床相关蓖麻毒素亚单位疫苗 RiVax 的佐剂的效果。αGalCer 具有很强的佐剂作用,表现在抗蓖麻毒素 IgG 滴度迅速升高,血清毒素中和活性迅速发展,以及在小鼠模型中增强对致死性蓖麻毒素的保护作用。这些结果突出了 αGalCer 增强针对设计用于中和蓖麻毒素的疫苗的保护性免疫反应的潜力,蓖麻毒素是一种快速作用的生物威胁剂。

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本文引用的文献

1
Progress and challenges associated with the development of ricin toxin subunit vaccines.蓖麻毒素亚单位疫苗研发的进展与挑战
Expert Rev Vaccines. 2016 Sep;15(9):1213-22. doi: 10.1586/14760584.2016.1168701. Epub 2016 Apr 6.
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Safety and immunogenicity of ricin vaccine, RVEc™, in a Phase 1 clinical trial.蓖麻毒素疫苗RVEc™在1期临床试验中的安全性和免疫原性。
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Comparative Adjuvant Effects of Type II Heat-Labile Enterotoxins in Combination with Two Different Candidate Ricin Toxin Vaccine Antigens.II型不耐热肠毒素与两种不同候选蓖麻毒素疫苗抗原联合使用的比较佐剂效应
Clin Vaccine Immunol. 2015 Dec;22(12):1285-93. doi: 10.1128/CVI.00402-15. Epub 2015 Oct 21.
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Thermostable ricin vaccine protects rhesus macaques against aerosolized ricin: Epitope-specific neutralizing antibodies correlate with protection.耐热蓖麻毒素疫苗可保护恒河猴免受雾化蓖麻毒素侵害:表位特异性中和抗体与保护作用相关。
Proc Natl Acad Sci U S A. 2015 Mar 24;112(12):3782-7. doi: 10.1073/pnas.1502585112. Epub 2015 Mar 9.
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Class-switched memory B cells remodel BCRs within secondary germinal centers.类别转换记忆 B 细胞在次级生发中心重塑 BCR。
Nat Immunol. 2015 Mar;16(3):296-305. doi: 10.1038/ni.3095. Epub 2015 Feb 2.
6
Combination of two candidate subunit vaccine antigens elicits protective immunity to ricin and anthrax toxin in mice.两种候选亚单位疫苗抗原的组合在小鼠中引发对蓖麻毒素和炭疽毒素的保护性免疫。
Vaccine. 2015 Jan 9;33(3):417-21. doi: 10.1016/j.vaccine.2014.11.036. Epub 2014 Dec 2.
7
Natural killer T cell and TLR9 agonists as mucosal adjuvants for sublingual vaccination with clade C HIV-1 envelope protein.自然杀伤T细胞和TLR9激动剂作为C组HIV-1包膜蛋白舌下疫苗接种的黏膜佐剂。
Vaccine. 2014 Dec 5;32(51):6934-6940. doi: 10.1016/j.vaccine.2014.10.051. Epub 2014 Nov 2.
8
Optimizing NKT cell ligands as vaccine adjuvants.优化自然杀伤T细胞配体作为疫苗佐剂。
Immunotherapy. 2014;6(3):309-20. doi: 10.2217/imt.13.175.
9
Natural killer T (NKT)-B-cell interactions promote prolonged antibody responses and long-term memory to pneumococcal capsular polysaccharides.自然杀伤 T(NKT)-B 细胞相互作用可促进对肺炎球菌荚膜多糖的延长抗体应答和长期记忆。
Proc Natl Acad Sci U S A. 2013 Oct 1;110(40):16097-102. doi: 10.1073/pnas.1303218110. Epub 2013 Sep 16.
10
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Clin Vaccine Immunol. 2013 Jun;20(6):789-94. doi: 10.1128/CVI.00098-13. Epub 2013 Mar 20.