Novel Mutant Phospholipase D from Hemiscorpius lepturus Acts as A Highly Immunogen in BALB/c Mice Against the Lethality of Scorpion Venom

Molecules

Abouzar Soleimani Moez¹  Reza H. Sajedi¹  Jean-Marc Sabatier²  Kamran Pooshang Bagheri³  Delavar Shahbazzadeh³ 

[1] Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran P.O. Box 14115-111, Iran;Institute of Neuro Physiopathology (INP), Université d’Aix-Marseille, UMR 7051, Faculté de Pharmacie, 27 Bd Jean Moulin, 13385 Marseille Cedex, France;Venom and Biotherapeutics Molecules Lab., Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran P.O. Box 13169-43351, Iran;

关键词: Hemiscorpius lepturus (H. lepturus);    phospholipase D (PLD);    Freund’s adjuvant;    alum adjuvant;    dermonecrosis;    vaccine;   

DOI  :  10.3390/molecules25071673

来源: DOAJ

【 摘 要 】

Hemiscorpius lepturus (H. lepturus) which belongs to the Scorpionidae family, is the deadliest scorpion in Iran. It causes pathological manifestations like dermonecrosis, hemolysis, renal failure, necrotic ulcers, and in some cases, even death. The venom of this scorpion is well-known for its cytotoxic effects in comparison with the other venomous scorpions which show significant neurotoxic effects. Due to the painless nature of the sting of this scorpion, the clinical symptoms occur in victims 24 to 72 h post-sting. In our previous studies during the last decade, we demonstrated that the medical complications are attributable to the presence of phospholipase D (PLD) as a major toxin in the venom. With the purpose of designing and constructing a vaccine against H. lepturus for humans, animal model experiments were performed. To achieve this goal, non-toxic PLD was developed by mutation of two critical catalytic residues—His12 and His48—into alanines and the product was then denominated mut-rPLD1. The in-vivo tests showed that the mice immunized with interval doses of 10 µg of mut-rPLD1, were completely protected against 10× the LD₁₀₀ of the venom. In conclusion, this mutant may be an effective vaccine candidate against scorpion envenomation by H. lepturus in future clinical studies.

【 授权许可】

Unknown