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

• Published in: Molecules (Basel, Switzerland) Switzerland), 2020-04, Vol.25 (7), p.1673
• Main Authors: Soleimani Moez, Abouzar, H Sajedi, Reza, Pooshang Bagheri, Kamran, Sabatier, Jean-Marc, Shahbazzadeh, Delavar
• Format: Article
• Language: English
• Subjects: Alanine; Alanine - metabolism; alum adjuvant; Amino Acid Substitution; Animal models; Animals; Arthropod Proteins; Arthropod Proteins - administration & dosage; Arthropod Proteins - genetics; Arthropod Proteins - immunology; Biochemistry, Molecular Biology; Biocompatibility; Cellular Biology; Complications; Cytotoxicity; dermonecrosis; Disease Models, Animal; Enzymes; Freund’s adjuvant; Habromys lepturus; Hemiscorpius lepturus (H. lepturus); Histidine; Histidine - metabolism; Immunization; Life Sciences; Male; Metabolites; Mice; Mutation; Neurotoxicity; Peptides; Phosphates; Phospholipase; Phospholipase D; phospholipase D (PLD); Phospholipase D - administration & dosage; Phospholipase D - genetics; Phospholipase D - immunology; Rabbits; Renal failure; Scorpion Venoms; Scorpion Venoms - adverse effects; Scorpion Venoms - immunology; Scorpions; Scorpions - enzymology; Scorpions - genetics; Software; Toxins; Ulcers; vaccine; Vaccines; Venom
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25071673

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 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 LD of the venom. In conclusion, this mutant may be an effective vaccine candidate against scorpion envenomation by in future clinical studies.