BACKGROUND Peanut allergy is a severe and increasingly frequent disease with high medical, psychosocial, and economic burden for affected patients and wider society. A causal, safe, and effective therapy is not yet available. OBJECTIVE We sought to develop an immunogenic, protective, and nonreactogenic vaccine candidate against peanut allergy based on virus-like particles (VLPs) coupled to single peanut allergens. METHODS To generate vaccine candidates, extracts of roasted peanut (Ara R) or the single allergens Ara h 1 or Ara h 2 were coupled to immunologically optimized Cucumber Mosaic Virus-derived VLPs (CuMVtt). BALB/c mice were sensitized intraperitoneally with peanut extract absorbed to alum. Immunotherapy consisted of a single subcutaneous injection of CuMVtt coupled to Ara R, Ara h 1, or Ara h 2. RESULTS The vaccines CuMVtt-Ara R, CuMVtt-Ara h 1, and CuMVtt-Ara h 2 protected peanut-sensitized mice against anaphylaxis after intravenous challenge with the whole peanut extract. Vaccines did not cause allergic reactions in sensitized mice. CuMVtt-Ara h 1 was able to induce specific IgG antibodies, diminished local reactions after skin prick tests, and reduced the infiltration of the gastrointestinal tract by eosinophils and mast cells after oral challenge with peanut. The ability of CuMVtt-Ara h 1 to protect against challenge with the whole extract was mediated by IgG, as shown via passive IgG transfer. FcγRIIb was required for protection, indicating that immune complexes with single allergens were able to block the allergic response against the whole extract, consisting of a complex allergen mixture. CONCLUSIONS Our data suggest that vaccination using single peanut allergens displayed on CuMVtt may represent a novel therapy against peanut allergy with a favorable safety profile.

中文翻译：

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基于显示单个主要花生过敏原的工程化病毒样颗粒，针对花生过敏的疫苗。

背景技术花生过敏是一种严重且日益频繁的疾病，对受影响的患者和更广泛的社会具有高的医学，心理和经济负担。尚无因果，安全和有效的疗法。目的我们试图基于偶联单个花生过敏原的病毒样颗粒（VLP）开发针对花生过敏的免疫原性，保护性和非反应性候选疫苗。方法为了产生候选疫苗，将烤花生（Ara R）或单一过敏原Ara h 1或Ara h 2的提取物与经免疫学优化的黄瓜花叶病毒衍生的VLP（CuMVtt）偶联。用吸收到明矾的花生提取物使BALB / c小鼠腹膜内致敏。免疫疗法由与Ara R，Ara h 1或Ara h 2偶联的单次CuMVtt皮下注射组成。结果疫苗CuMVtt-Ara R，CuMVtt-Ara h 1和CuMVtt-Ara h 2在用全花生提取物静脉内攻击后，保护了花生敏感的小鼠免于过敏反应。疫苗不会在致敏小鼠中引起过敏反应。CuMVtt-Ara h 1能够诱导特异性IgG抗体，减少皮肤点刺试验后的局部反应，并减少了口服花生米挑战后嗜酸性粒细胞和肥大细胞对胃肠道的浸润。如通过被动IgG转移所显示的，CuMVtt-Ara h 1抵抗整个提取物攻击的能力由IgG介导。FcγRIIb是保护所必需的，这表明具有单一过敏原的免疫复合物能够阻止针对整个提取物的过敏反应，该提取物由复杂的过敏原混合物组成。