Benazzouz Safouane M, Benlouahmia Nesrine, Bouhadida Karima, Benlamara Meriem, Arezki Naziha, Sadeddine Oum El Kheir, Issad Mourad, Attal Nabila, Mansouri Kamel, Derrar Fawzi, Djidjik Reda
Laboratoire de Pharmacologie, Faculté de Pharmacie d'Alger, Université d'Alger 1. 8 Rue du Lieutenant Mohamed Benarfa, El Biar, Alger 16000, Algeria.
Laboratoire des Sérums Thérapeutiques, Département des Produits Biologiques Humains, Direction de la Production, Institut Pasteur d'Algérie. Rue du Petit Staoueli, Dely Ibrahim, Alger 16320, Algeria.
Vaccine X. 2024 May 25;19:100503. doi: 10.1016/j.jvacx.2024.100503. eCollection 2024 Aug.
Scorpion envenoming (SE) is a public health problem in developing countries. In Algeria, the population exposed to the risk of SE was estimated at 86.45% in 2019. Thus, the development of a vaccine to protect the exposed population against scorpion toxins would be a major advance in the fight against this disease. This work aimed to evaluate the immunoprotective effect of a Multiple Antigenic Peptide against the Aah II toxin of scorpion, the most dangerous scorpion species in Algeria. The immunogen MAP1Aah2 was designed and tested accordingly. This molecule contains a B epitope, derived from Aah II toxin, linked by a spacer to a universal T epitope, derived from the tetanus toxin. The results showed that MAP1Aah2 was non-toxic despite the fact that its sequence was derived from Aah II toxin. The immunoenzymatic assay revealed that the 3 immunization regimens tested generated specific anti-MAP1Aah2 antibodies and cross-reacted with the toxin. Mice immunized with this immunogen were partially protected against mortality caused by challenge doses of 2 and 3 LD of the toxin. The survival rate and developed symptoms varied depending on the adjuvant and the challenge dose used. In the neutralization test, the immune sera of mice having received the immunogen with incomplete Freund's adjuvant neutralized a challenge dose of 2 LD50. Hence, the concept of using peptide dendrimers, based on linear epitopes of scorpion toxins, as immunogens against the parent toxin was established. However, the protective properties of the tested immunogen require further optimizations.
蝎子蜇伤(SE)在发展中国家是一个公共卫生问题。在阿尔及利亚,2019年暴露于蝎子蜇伤风险的人口估计为86.45%。因此,开发一种疫苗来保护暴露人群免受蝎子毒素侵害将是抗击这种疾病的一项重大进展。这项工作旨在评估一种多抗原肽对阿尔及利亚最危险的蝎子物种的Aah II毒素的免疫保护作用。相应地设计并测试了免疫原MAP1Aah2。该分子包含一个源自Aah II毒素的B表位,通过间隔区与一个源自破伤风毒素的通用T表位相连。结果表明,尽管MAP1Aah2的序列源自Aah II毒素,但它无毒。免疫酶测定显示,所测试的3种免疫方案产生了特异性抗MAP1Aah2抗体,并与毒素发生交叉反应。用这种免疫原免疫的小鼠对2倍和3倍致死剂量毒素的攻击引起的死亡有部分保护作用。存活率和出现的症状因佐剂和所用攻击剂量而异。在中和试验中,接受含不完全弗氏佐剂免疫原的小鼠免疫血清中和了2倍半数致死剂量的攻击剂量。因此,基于蝎子毒素线性表位的肽树枝状大分子作为针对亲本毒素的免疫原的概念得以确立。然而,所测试免疫原的保护特性需要进一步优化。