McGowen Afton L, Hale Laura P, Shelburne Christopher P, Abraham Soman N, Staats Herman F
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
Vaccine. 2009 Jun 2;27(27):3544-52. doi: 10.1016/j.vaccine.2009.03.069. Epub 2009 Apr 14.
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.
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。