Abstract:
Food allergy (FA) is estimated to impact up to 10% of the population and is a growing health concern. FA results from a failure in the mucosal immune system to establish or maintain immunological tolerance to innocuous dietary antigens, IgE production, and the release of histamine and other mediators upon exposure to a food allergen. Of the different FAs, peanut allergy has the highest incidence of severe allergic responses, including systemic anaphylaxis. Despite the recent FDA approval of peanut oral immunotherapy and other investigational immunotherapies, a loss of protection following cessation of therapy can occur, suggesting that these therapies do not address the underlying immune response driving FA. Our lab has shown that liver-directed gene therapy with an adeno-associated virus (AAV) vector induces transgene product-specific regulatory T cells (Tregs), eradicates pre-existing pathogenic antibodies, and protects against anaphylaxis in several models, including ovalbumin induced FA. In an epicutaneous peanut allergy mouse model, the hepatic AAV co-expression of four peanut antigens Ara h1, Ara h2, Ara h3, and Ara h6 together or the single expression of Ara h3 prevented the development of a peanut allergy. Since FA patients show a reduction in Treg numbers and/or function, we believe our approach may address this unmet need.
摘要:
食物过敏(FA)估计会影响多达10%的人口,并且是一个日益严重的健康问题。FA是由粘膜免疫系统无法建立或维持对无害饮食抗原的免疫耐受引起的。IgE生产,以及暴露于食物过敏原后释放组胺和其他介质。在不同的FA中,花生过敏的严重过敏反应发生率最高,包括全身过敏反应.尽管最近FDA批准了花生口服免疫疗法和其他研究性免疫疗法,停止治疗后可能会失去保护,这表明这些疗法不能解决驱动FA的潜在免疫反应。我们的实验室已经表明,肝定向基因治疗与腺相关病毒(AAV)载体诱导转基因产物特异性调节性T细胞(Tregs),根除预先存在的致病性抗体,并在几种模型中防止过敏反应,包括卵清蛋白诱导的FA。在表皮花生过敏小鼠模型中,四种花生抗原Arah1,Arah2,Arah3和Arah6的肝AAV共表达或Arah3的单一表达阻止了花生过敏的发展。由于FA患者显示Treg数量和/或功能减少,我们相信我们的方法可能会解决这个未满足的需求。