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肥大细胞激活剂化合物48/80用作炭疽芽孢杆菌保护性抗原皮内免疫佐剂时安全有效。

The mast cell activator compound 48/80 is safe and effective when used as an adjuvant for intradermal immunization with Bacillus anthracis protective antigen.

作者信息

McGowen Afton L, Hale Laura P, Shelburne Christopher P, Abraham Soman N, Staats Herman F

机构信息

Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.

出版信息

Vaccine. 2009 Jun 2;27(27):3544-52. doi: 10.1016/j.vaccine.2009.03.069. Epub 2009 Apr 14.

Abstract

We evaluated the safety and efficacy of the mast cell activator compound 48/80 (C48/80) when used as an adjuvant delivered intradermally (ID) with recombinant anthrax protective antigen (rPA) in comparison with two well-known adjuvants. Mice were vaccinated in the ear pinnae with rPA or rPA+C48/80, CpG oligodeoxynucleotides (CpG), or cholera toxin (CT). All adjuvants induced similar increases in serum anti-rPA IgG and lethal toxin neutralizing antibodies. C48/80 induced a balanced cytokine production (Th1/Th2/Th17) by antigen-restimulated splenocytes, minimal injection site inflammation, and no antigen-specific IgE. Histological analysis demonstrated that vaccination with C48/80 reduced the number of resident mast cells and induced an injection site neutrophil influx within 24h. Our data demonstrate that C48/80 is a safe and effective adjuvant, when used by the intradermal route, to induce protective antibody and balanced Th1/Th2/Th17 responses.

摘要

我们评估了肥大细胞激活剂化合物48/80(C48/80)与两种知名佐剂相比,皮内注射(ID)重组炭疽保护性抗原(rPA)时作为佐剂的安全性和有效性。用rPA或rPA + C48/80、CpG寡脱氧核苷酸(CpG)或霍乱毒素(CT)对小鼠耳廓进行疫苗接种。所有佐剂均诱导血清抗rPA IgG和致死毒素中和抗体出现相似程度的增加。C48/80通过抗原再刺激的脾细胞诱导了平衡的细胞因子产生(Th1/Th2/Th17),注射部位炎症轻微,且未产生抗原特异性IgE。组织学分析表明,接种C48/80可减少驻留肥大细胞数量,并在24小时内诱导注射部位中性粒细胞流入。我们的数据表明,皮内使用C48/80作为佐剂可诱导保护性抗体和平衡的Th1/Th2/Th17反应,是一种安全有效的佐剂。

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