Pediatric Allergy and Immunology, Icahn School of Medicine at Mount Sinai, New York, NY; Jaffe Food Allergy Institute, New York, NY.
Department of Biomedical Engineering, Yale University, New Haven, Conn.
J Allergy Clin Immunol. 2016 Aug;138(2):536-543.e4. doi: 10.1016/j.jaci.2016.01.047. Epub 2016 Apr 26.
BACKGROUND: Treatments to reverse peanut allergy remain elusive. Current clinical approaches using peanut oral/sublingual immunotherapy are promising, but concerns about safety and long-term benefit remain a barrier to wide use. Improved methods of delivering peanut-specific immunotherapy are needed. OBJECTIVE: We sought to investigate the efficacy and safety of peanut oral immunotherapy using CpG-coated poly(lactic-co-glycolic acid) nanoparticles containing peanut extract (CpG/PN-NPs) in a murine model of peanut allergy. METHODS: C3H/HeJ mice were rendered peanut allergic by means of oral sensitization with peanut and cholera toxin. Mice were then subjected to 4 weekly gavages with CpG/PN-NPs, vehicle (PBS), nanoparticles alone, peanut alone, CpG nanoparticles, or peanut nanoparticles. Untreated mice served as naive controls. After completing therapy, mice underwent 5 monthly oral peanut challenges. Anaphylaxis was evaluated by means of visual assessment of symptom scores and measurement of body temperature and plasma histamine levels. Peanut-specific serum IgE, IgG1, and IgG2a levels were measured by using ELISA, as were cytokine recall responses in splenocyte cultures. RESULTS: Mice with peanut allergy treated with CpG/PN-NPs but not vehicle or other treatment components were significantly protected from anaphylaxis to all 5 oral peanut challenges, as indicated by lower symptom scores, less change in body temperature, and a lower increase of plasma histamine levels. Importantly, CpG/PN-NP treatment did not cause anaphylactic reactions. Treatment was associated with a sustained and significant decrease in peanut-specific IgE/IgG1 levels and an increase in peanut-specific IgG2a levels. Compared with vehicle control animals, peanut recall responses in splenocyte cultures from nanoparticle-treated mice showed significantly decreased levels of TH2 cytokines (IL-4, IL-5, and IL-13) but increased IFN-γ levels in cell supernatants. CONCLUSIONS: Preclinical findings indicate that peanut oral immunotherapy with CpG/PN-NPs might be a valuable strategy for peanut-specific immunotherapy in human subjects.
背景：逆转花生过敏的治疗方法仍难以捉摸。目前使用花生口服/舌下免疫疗法的临床方法很有前景，但对安全性和长期益处的担忧仍是广泛应用的障碍。需要改进的方法来提供花生特异性免疫疗法。
目的：我们试图研究使用含有花生提取物的 CpG 包被聚（乳酸-共-乙醇酸）纳米颗粒（CpG/PN-NPs）在花生过敏的小鼠模型中的花生口服免疫疗法的疗效和安全性。
方法：通过用花生和霍乱毒素口服致敏，使 C3H/HeJ 小鼠产生花生过敏。然后，将小鼠用 4 周的 CpG/PN-NPs、载体（PBS）、单独的纳米颗粒、单独的花生、CpG 纳米颗粒或花生纳米颗粒进行灌胃。未治疗的小鼠作为对照。完成治疗后，小鼠接受 5 次每月的口服花生挑战。通过视觉评估症状评分和测量体温和血浆组胺水平来评估过敏反应。通过 ELISA 测量花生特异性血清 IgE、IgG1 和 IgG2a 水平，并在脾细胞培养物中测量细胞因子回忆反应。
结果：用 CpG/PN-NPs 治疗但未用载体或其他治疗成分治疗的花生过敏小鼠在所有 5 次口服花生挑战中均显著免受过敏反应，表现为症状评分较低、体温变化较小和血浆组胺水平升高较低。重要的是，CpG/PN-NP 治疗不会引起过敏反应。治疗与花生特异性 IgE/IgG1 水平的持续显著降低和花生特异性 IgG2a 水平的增加相关。与载体对照动物相比，来自纳米颗粒处理小鼠的脾细胞培养物中的花生回忆反应显示出 TH2 细胞因子（IL-4、IL-5 和 IL-13）水平显著降低，但细胞上清液中的 IFN-γ 水平增加。
结论：临床前发现表明，CpG/PN-NPs 进行的花生口服免疫疗法可能是人类花生特异性免疫治疗的一种有价值的策略。
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