Jacquet Alain, Vanderschrick Jean-François, Vandenbranden Michel, Elouahabi Abdelatif, Magi Mauro, Garcia Lida, Ruysschaert Jean-Marie
Service de Génétique Appliquée, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, Rue des Professeurs Jeener et Brachet, 12, B-6041 Gosselies, Belgium.
Mol Ther. 2005 Jun;11(6):960-8. doi: 10.1016/j.ymthe.2004.12.024.
The present study evaluated the prophylactic potential of ProDer p 1, the recombinant precursor form of the major mite allergen Der p 1, combined with the cationic lipid diC14-amidine in a murine model of house dust mite allergy. Naive mice vaccinated with the amidine/allergen complex developed a Th1-biased immune response characterized by the absence of specific IgE, the production of specific IgG2a, and the presence of IFN-gamma in splenocyte cultures. In contrast, ProDer p 1 adjuvanted with alum induced typical strictly Th2-biased allergic responses with strong IgG1 and IgE titers and IL-5 secretion. Removal of negatively charged sialic acids in ProDer p 1 or increasing the ionic strength reduced the binding of ProDer p 1 to the cationic liposomes and resulted in a decrease of the allergen immunogenicity, suggesting that complexation is required for triggering an optimal immune response. Finally, prophylactic vaccination with ProDer p 1-diC14-amidine reduced drastically the production of specific IgE and airway eosinophilia following subsequent immunization with Der p 1-alum and challenge with aerosolized house dust mite extracts. In conclusion, recombinant ProDer p 1 complexed with diC14-amidine could represent an efficient prophylactic vaccine against house dust mite allergy.
本研究在屋尘螨过敏的小鼠模型中评估了主要螨过敏原Der p 1的重组前体形式ProDer p 1与阳离子脂质二C14 - 脒联合使用的预防潜力。用脒/过敏原复合物接种的未致敏小鼠产生了以缺乏特异性IgE、产生特异性IgG2a以及脾细胞培养物中存在干扰素 - γ为特征的Th1偏向性免疫反应。相比之下,用明矾佐剂的ProDer p 1诱导了典型的严格Th2偏向性过敏反应,具有高IgG1和IgE滴度以及IL - 5分泌。去除ProDer p 1中带负电荷的唾液酸或增加离子强度会降低ProDer p 1与阳离子脂质体的结合,并导致过敏原免疫原性降低,这表明形成复合物对于触发最佳免疫反应是必需的。最后,用ProDer p 1 - 二C14 - 脒进行预防性疫苗接种,在随后用Der p 1 - 明矾免疫并用雾化屋尘螨提取物攻击后,显著降低了特异性IgE的产生和气道嗜酸性粒细胞增多。总之,与二C14 - 脒复合的重组ProDer p 1可能代表一种有效的抗屋尘螨过敏预防性疫苗。