Center of Excellence in Vaccine Research and Development, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Curr Opin Allergy Clin Immunol. 2021 Dec 1;21(6):569-575. doi: 10.1097/ACI.0000000000000772.
Molecular forms of allergen-specific immunotherapy (AIT) are continuously emerging to improve the efficacy of the treatment, to shorten the duration of protocols and to prevent any side effects. The present review covers the recent progress in the development of AIT based on nucleic acid encoding allergens or CpG oligodeoxynucleotides (CpG-ODN).
Therapeutic vaccinations with plasmid deoxyribonucleic acid (DNA) encoding major shrimp Met e 1 or insect For t 2 allergen were effective for the treatment of food or insect bite allergy in respective animal models. DNA expressing hypoallergenic shrimp tropomyosin activated Foxp3+ T regulatory (Treg) cells whereas DNA encoding For t 2 down-regulated the expression of pruritus-inducing IL-31. Co-administrations of major cat allergen Fel d 1 with high doses of CpG-ODN reduced Th2 airway inflammation through tolerance induction mediated by GATA3+ Foxp3hi Treg cells as well as early anti-inflammatory TNF/TNFR2 signaling cascade. Non-canonical CpG-ODN derived from Cryptococcus neoformans as well as methylated CpG sites present in the genomic DNA from Bifidobacterium infantis mediated Th1 or Treg cell differentiation respectively.
Recent studies on plasmid DNA encoding allergens evidenced their therapeutic potential for the treatment of food allergy and atopic dermatitis. Unmethylated or methylated CpG-ODNs were shown to activate dose-dependent Treg/Th1 responses. Large clinical trials need to be conducted to confirm these promising preclinical data. Moreover, tremendous success of messenger ribonucleic acid (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 must encourage as well the re-exploration of mRNA vaccine platform for innovative AIT.
变应原特异性免疫治疗(AIT)的分子形式不断涌现,旨在提高治疗效果、缩短方案持续时间并预防任何副作用。本综述涵盖了基于核酸编码变应原或 CpG 寡脱氧核苷酸(CpG-ODN)的 AIT 最新进展。
编码主要虾过敏原 Met e 1 或昆虫过敏原 For t 2 的质粒脱氧核糖核酸(DNA)的治疗性疫苗在各自的动物模型中对食物或昆虫叮咬过敏的治疗有效。表达低变应原性虾肌球蛋白的 DNA 激活了 Foxp3+T 调节(Treg)细胞,而编码 For t 2 的 DNA 下调了瘙痒诱导的白细胞介素 31 的表达。高剂量 CpG-ODN 与主要猫过敏原 Fel d 1 共同给药可通过 GATA3+Foxp3hiTreg 细胞介导的耐受诱导以及早期抗炎 TNF/TNFR2 信号级联减少 Th2 气道炎症。来自新型隐球菌的非典型 CpG-ODN 以及双歧杆菌基因组 DNA 中存在的甲基化 CpG 位点分别介导 Th1 或 Treg 细胞分化。
编码过敏原的质粒 DNA 的最近研究证明了它们在治疗食物过敏和特应性皮炎方面的治疗潜力。未甲基化或甲基化的 CpG-ODN 被证明可激活剂量依赖性的 Treg/Th1 反应。需要进行大型临床试验来证实这些有前景的临床前数据。此外,信使核糖核酸(mRNA)疫苗对抗严重急性呼吸综合征冠状病毒 2 的巨大成功也必须鼓励重新探索 mRNA 疫苗平台以进行创新的 AIT。