Zenouaki I, Kharrat R, Sabatier J M, Devaux C, Karoui H, Van Rietschoten J, el Ayeb M, Rochat H
Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, Tunisia.
Vaccine. 1997 Feb;15(2):187-94. doi: 10.1016/s0264-410x(97)00144-8.
A synthetic peptide mimicking the North African scorpion Androctonus australis hector toxin II was designed and produced by chemical solid-phase synthesis. It contains the entire sequence of toxin II (64 amino acid residues), with each half-cystine being replaced by the isosteric residue a-aminobutyric acid, and was thus devoid of disulfide bridges. This construct was totally nontoxic in mice even if large amounts, equivalent to 1000 times the LD50 of the original toxin, were injected by the intracerebroventricular route. The synthetic peptide, either as a monomer or polymerized by means of glutaraldehyde, induced the production of antitoxin neutralizing antibodies in immunized mice and rabbits. After three injections with either the monomeric or polymerized synthetic peptide, the immunized mice were protected against several lethal doses of the corresponding native toxin or scorpion venom. Six months after immunization, the mice were completely protected against challenge with eight LD50 of the original toxin. The protection was better when the polymerized synthetic peptide was used. One month after the start of the immunization program, it showed a good correlation between antibody titer and protection. However, antibody titer decreased with time but protection remained high. This suggests that additional factors other than circulating antibodies play a role in protective activity.
设计并通过化学固相合成制备了一种模拟北非蝎子澳链尾蝎毒素II的合成肽。它包含毒素II的完整序列（64个氨基酸残基），每个半胱氨酸被等排残基α-氨基丁酸取代，因此没有二硫键。即使通过脑室内途径注射大量相当于原始毒素半数致死量1000倍的该构建体，在小鼠中也完全无毒。该合成肽无论是单体形式还是通过戊二醛聚合后，均可在免疫的小鼠和兔子中诱导产生抗毒素中和抗体。用单体或聚合的合成肽进行三次注射后，免疫的小鼠可免受几种致死剂量的相应天然毒素或蝎毒的侵害。免疫六个月后，小鼠完全受到保护，可抵御八倍原始毒素半数致死量的攻击。使用聚合的合成肽时保护效果更好。免疫程序开始一个月后，抗体滴度与保护作用之间呈现良好的相关性。然而，抗体滴度随时间下降，但保护作用仍然很高。这表明除循环抗体外的其他因素在保护活性中起作用。
