Nouri Abdelmounaim, Laraba-Djebari Fatima
USTHB, Faculty of Biological Sciences; Laboratory of Cellular and Molecular Biology, BP 32 El-Alia, Bab Ezzouar, Algiers, Algeria.
USTHB, Faculty of Biological Sciences; Laboratory of Cellular and Molecular Biology, BP 32 El-Alia, Bab Ezzouar, Algiers, Algeria.
Vaccine. 2015 Oct 26;33(43):5756-5763. doi: 10.1016/j.vaccine.2015.09.045. Epub 2015 Sep 28.
Envenomation is a public health problem in many regions of the world. The only available treatment is the serotherapy that has limited efficiency due to the delay of its administration. The goal of this study is to provide a new and more efficient alternative to this treatment. A comparative study of the effects of two adjuvants in their ability to enhance the efficiency of the detoxified and safe antigens to produce a long lasting immunoprotection is undertaken using Aluminum Hydroxide adjuvant (Alum) or the water-in-oil MF59 adjuvant mixed with Androctonus australis hector (Aah) detoxified venom, and compare their effects on the immune system. Immunization schedule was performed with two groups of rabbits, which were injected with attenuated venom and Alum or MF59 adjuvant preparations, once a month during three months. Blood samples were collected each week for cell count, evaluation of myeloperoxidase (MPO) and eosinoperoxydase (EPO) activities and antibody titer. After four months from the last immunization, rabbits were challenged with increased doses of native Aah venom. Results showed that MF59 effect was immediate in the first 24h post-immunization by activating the recruitment of lymphocytes, monocytes and neutrophils, while Alum adjuvant effect seems to be delayed, and appeared in the second week after immunization. An important cell infiltration was observed with Alum preparation, due to its specific local depot effect. However, immunized animals with MF59 preparation challenged with the native venom showed a protective effect against its toxicity until 6 LD50 compared to those immunized with Alum preparation which are only protected at 4 LD50. One week after challenge, only immunized animals with Alum preparation present an increase in cell infiltration, MPO and EPO activities. These results are correlated with the ability of MF59 adjuvant to induce a potent immunoprotective effect against Aah venom compared to Alum adjuvant.
在世界许多地区，蛇咬伤中毒是一个公共卫生问题。目前唯一可用的治疗方法是血清疗法，但由于给药延迟，其疗效有限。本研究的目的是提供一种新的、更有效的替代治疗方法。使用氢氧化铝佐剂（明矾）或与澳毒蛛（Aah）解毒毒液混合的油包水乳剂MF59佐剂，对两种佐剂增强解毒且安全的抗原产生持久免疫保护能力的效果进行比较研究，并比较它们对免疫系统的影响。对两组兔子进行免疫接种，每月注射一次减毒毒液和明矾或MF59佐剂制剂，持续三个月。每周采集血样进行细胞计数、髓过氧化物酶（MPO）和嗜酸性粒细胞过氧化物酶（EPO）活性评估以及抗体效价检测。在最后一次免疫四个月后，用增加剂量的天然Aah毒液对兔子进行攻击。结果显示，MF59在免疫后最初24小时通过激活淋巴细胞、单核细胞和中性粒细胞的募集产生即时效应，而明矾佐剂的效应似乎延迟出现，在免疫后第二周出现。由于其特定的局部储存效应，明矾制剂观察到重要的细胞浸润。然而，用天然毒液攻击的MF59制剂免疫动物对其毒性表现出保护作用，直至6倍半数致死量（LD50），而用明矾制剂免疫的动物仅在4倍LD50时受到保护。攻击一周后，只有用明矾制剂免疫的动物出现细胞浸润、MPO和EPO活性增加。这些结果与MF59佐剂相比明矾佐剂诱导针对Aah毒液的有效免疫保护作用的能力相关。
