CpG Adjuvant in Allergen-Specific Immunotherapy: Finding the Sweet Spot for the Induction of Immune Tolerance.
CpG Adjuvant in Allergen-Specific Immunotherapy: Finding the Sweet Spot for the Induction of Immune Tolerance.
复制标题
CpG佐剂在过敏原特异性免疫治疗中的应用：寻找诱导免疫耐受的最佳点。
DOI：
10.3389/fimmu.2021.590054
复制
发表时间：
2021
影响因子：
7.3
通讯作者：
Ollert M
中科院分区：
文献类型：
--
作者：
Montamat G;Leonard C;Poli A;Klimek L;Ollert M
过去几年，发达国家和发展中国家 IgE 介导的过敏性疾病的患病率和发病率有所增加。过敏原特异性免疫疗法（AIT）是目前唯一可用于治疗过敏性疾病且具有长期疗效的治疗方法。尽管 AIT 从一开始就被证明是一种成功的免疫调节疗法，但如今它仍然面临着一些未满足的需求和挑战。例如，一些患者可能会出现严重的副作用，而另一些患者则无反应，而延长治疗计划可能会导致患者缺乏依从性和治疗中断。改善 AIT 的常见策略依赖于使用佐剂和免疫调节剂来增强其效果并提高其安全性。在测试其临床功效的佐剂中，CpG 寡脱氧核苷酸 (CpG-ODN) 的研究取得了有限的成功，并且尚未达到临床过敏治疗的 III 期试验。然而，最近发现的 CpG-ODN 的免疫耐受促进特性使这种佐剂作为治疗过敏性疾病的免疫调节剂再次处于突出地位。事实上，研究表明，CpG-ODN 剂量和浓度对于通过招募 pDC 来促进免疫调节至关重要。虽然低剂量会引起炎症反应，但高剂量的 CpG-ODN 会引发耐受性反应，从而逆转预先建立的过敏环境。一致地，CpG-ODN 还被发现可以刺激产生 IL-10 的 B 细胞，即所谓的 B 调节细胞 (Bregs)。因此，CpG-ODN 在多种动物模型中显示出其预防和恢复过敏反应的能力，显示出其作为 IgE 介导的过敏的预防性和主动治疗的潜力。在这篇综述中，我们描述了基于 CpG-ODN 的过敏性疾病疗法，尽管过去取得了有限的成功，但仍然可以在 AIT 背景下进一步用作佐剂或免疫调节剂，值得额外关注。在这里，我们讨论过去和当前的知识，其中强调 CpG-ODN 作为一种潜在的佐剂，在适当的条件和配方下使用时，可以重新评估其增强 AIT 的效果。
Prevalence and incidence of IgE-mediated allergic diseases have increased over the past years in developed and developing countries. Allergen-specific immunotherapy (AIT) is currently the only curative treatment available for allergic diseases that has long-term efficacy. Although AIT has been proven successful as an immunomodulatory therapy since its beginnings, it still faces several unmet needs and challenges today. For instance, some patients can experience severe side effects, others are non-responders, and prolonged treatment schedules can lead to lack of patient adherence and therapy discontinuation. A common strategy to improve AIT relies on the use of adjuvants and immune modulators to boost its effects and improve its safety. Among the adjuvants tested for their clinical efficacy, CpG oligodeoxynucleotide (CpG-ODN) was investigated with limited success and without reaching phase III trials for clinical allergy treatment. However, recently discovered immune tolerance-promoting properties of CpG-ODN place this adjuvant again in a prominent position as an immune modulator for the treatment of allergic diseases. Indeed, it has been shown that the CpG-ODN dose and concentration are crucial in promoting immune regulation through the recruitment of pDCs. While low doses induce an inflammatory response, high doses of CpG-ODN trigger a tolerogenic response that can reverse a pre-established allergic milieu. Consistently, CpG-ODN has also been found to stimulate IL-10 producing B cells, so-called B regulatory cells (Bregs). Accordingly, CpG-ODN has shown its capacity to prevent and revert allergic reactions in several animal models showing its potential as both preventive and active treatment for IgE-mediated allergy. In this review, we describe how CpG-ODN-based therapies for allergic diseases, despite having shown limited success in the past, can still be exploited further as an adjuvant or immune modulator in the context of AIT and deserves additional attention. Here, we discuss the past and current knowledge, which highlights CpG-ODN as a potential adjuvant to be reevaluated for the enhancement of AIT when used in appropriate conditions and formulations.