Albrecht Melanie, Suezer Yasemin, Staib Caroline, Sutter Gerd, Vieths Stefan, Reese Gerald
Paul-Ehrlich-Institut, Department of Allergology, Langen, Germany.
J Gene Med. 2008 Dec;10(12):1324-33. doi: 10.1002/jgm.1256.
Currently, no treatment is available for food allergy and strict avoidance of the allergenic food remains the only way to manage the allergy. New strategies leading to a safe and efficacious food allergy treatment are required. Modified vaccinia virus Ankara (MVA), which allows high levels of expression of recombinant protein in vivo and gives rise to a Th1-biased specific immune response, was used as a prophylactic vaccine in a murine model of ovalbumin (OVA) allergy.
An MVA-OVA vector vaccine was prepared. Female BALB/c mice were vaccinated twice with a MVA-OVA vector vaccine, followed by sensitization with OVA plus alum. OVA-specific immunoglobulin E(IgE) activity was measured by mediator release from rat basophilic leukaemia cells, whereas specific IgG subclass titers were determined by enzyme-linked immunosorbent assay.
Expression of immunological active OVA in mammalian cells was demonstrated. OVA-specific IgE levels in sera from MVA-OVA-vaccinated mice were reduced and appeared delayed. The vaccine-mediated immune modulation was dose-dependent; the highest vaccine dose protected 50% of the animals from allergic sensitization. Upon sensitization, similar OVA-specific IgG1 titers were found in all mice, but the OVA-specific IgG2a antibody levels were strongly increased in MVA-OVA-vaccinated mice, signifying a Th1-biased and, non-allergic immune response.
Prophylactic vaccination with MVA-OVA delays and in part even prevents the onset of a successful allergen-specific sensitization. Recombinant MVA, which fulfills the requirements for clinical application, is a promising candidate vector for the development of novel approaches to allergen-specific prophylactic vaccination and specific immunotherapy.
目前，食物过敏尚无有效治疗方法，严格避免食用致敏食物仍是控制过敏的唯一途径。因此，需要研发新的策略来实现安全有效的食物过敏治疗。安卡拉痘苗病毒（MVA）可在体内高水平表达重组蛋白，并引发以Th1为主的特异性免疫反应，本研究将其作为卵清蛋白（OVA）过敏小鼠模型的预防性疫苗。
制备MVA-OVA载体疫苗。雌性BALB/c小鼠用MVA-OVA载体疫苗免疫两次，随后用OVA加明矾进行致敏。通过大鼠嗜碱性白血病细胞释放介质来测定OVA特异性免疫球蛋白E（IgE）活性，而特异性IgG亚类滴度则通过酶联免疫吸附测定法测定。
证实了免疫活性OVA在哺乳动物细胞中的表达。接种MVA-OVA疫苗小鼠血清中的OVA特异性IgE水平降低且出现延迟。疫苗介导的免疫调节呈剂量依赖性；最高疫苗剂量可保护50%的动物免于过敏致敏。致敏后，所有小鼠的OVA特异性IgG1滴度相似，但接种MVA-OVA疫苗的小鼠中OVA特异性IgG2a抗体水平显著升高，表明是一种以Th1为主的非过敏性免疫反应。
用MVA-OVA进行预防性疫苗接种可延迟甚至部分预防成功的过敏原特异性致敏的发生。重组MVA满足临床应用要求，是开发新型过敏原特异性预防性疫苗接种和特异性免疫治疗方法的有前景的候选载体。
