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

<i>Hemiscorpius lepturus (H. lepturus)</i> 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-k...

Full description

Bibliographic Details
Main Authors: Abouzar Soleimani Moez, Reza H. Sajedi, Kamran Pooshang Bagheri, Jean-Marc Sabatier, Delavar Shahbazzadeh
Format: Article
Language:English
Published: MDPI AG 2020-04-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/25/7/1673
_version_ 1797571486180966400
author Abouzar Soleimani Moez
Reza H. Sajedi
Kamran Pooshang Bagheri
Jean-Marc Sabatier
Delavar Shahbazzadeh
author_facet Abouzar Soleimani Moez
Reza H. Sajedi
Kamran Pooshang Bagheri
Jean-Marc Sabatier
Delavar Shahbazzadeh
author_sort Abouzar Soleimani Moez
collection DOAJ
description <i>Hemiscorpius lepturus (H. lepturus)</i> 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 <i>H. lepturus</i> 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<sub>100</sub> of the venom. In conclusion, this mutant may be an effective vaccine candidate against scorpion envenomation by <i>H. lepturus</i> in future clinical studies.
first_indexed 2024-03-10T20:40:23Z
format Article
id doaj.art-c3432b1e788f46d381a8ad58c35154c4
institution Directory Open Access Journal
issn 1420-3049
language English
last_indexed 2024-03-10T20:40:23Z
publishDate 2020-04-01
publisher MDPI AG
record_format Article
series Molecules
spelling doaj.art-c3432b1e788f46d381a8ad58c35154c42023-11-19T20:43:44ZengMDPI AGMolecules1420-30492020-04-01257167310.3390/molecules25071673Novel Mutant Phospholipase D from <i>Hemiscorpius lepturus</i> Acts as A Highly Immunogen in BALB/c Mice Against the Lethality of Scorpion VenomAbouzar Soleimani Moez0Reza H. Sajedi1Kamran Pooshang Bagheri2Jean-Marc Sabatier3Delavar Shahbazzadeh4Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran P.O. Box 14115-111, IranDepartment of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran P.O. Box 14115-111, IranVenom and Biotherapeutics Molecules Lab., Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran P.O. Box 13169-43351, IranInstitute of Neuro Physiopathology (INP), Université d’Aix-Marseille, UMR 7051, Faculté de Pharmacie, 27 Bd Jean Moulin, 13385 Marseille Cedex, FranceVenom and Biotherapeutics Molecules Lab., Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran P.O. Box 13169-43351, Iran<i>Hemiscorpius lepturus (H. lepturus)</i> 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 <i>H. lepturus</i> 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<sub>100</sub> of the venom. In conclusion, this mutant may be an effective vaccine candidate against scorpion envenomation by <i>H. lepturus</i> in future clinical studies.https://www.mdpi.com/1420-3049/25/7/1673<i>Hemiscorpius lepturus (H. lepturus)</i>phospholipase D (PLD)Freund’s adjuvantalum adjuvantdermonecrosisvaccine
spellingShingle Abouzar Soleimani Moez
Reza H. Sajedi
Kamran Pooshang Bagheri
Jean-Marc Sabatier
Delavar Shahbazzadeh
Novel Mutant Phospholipase D from <i>Hemiscorpius lepturus</i> Acts as A Highly Immunogen in BALB/c Mice Against the Lethality of Scorpion Venom
Molecules
<i>Hemiscorpius lepturus (H. lepturus)</i>
phospholipase D (PLD)
Freund’s adjuvant
alum adjuvant
dermonecrosis
vaccine
title Novel Mutant Phospholipase D from <i>Hemiscorpius lepturus</i> Acts as A Highly Immunogen in BALB/c Mice Against the Lethality of Scorpion Venom
title_full Novel Mutant Phospholipase D from <i>Hemiscorpius lepturus</i> Acts as A Highly Immunogen in BALB/c Mice Against the Lethality of Scorpion Venom
title_fullStr Novel Mutant Phospholipase D from <i>Hemiscorpius lepturus</i> Acts as A Highly Immunogen in BALB/c Mice Against the Lethality of Scorpion Venom
title_full_unstemmed Novel Mutant Phospholipase D from <i>Hemiscorpius lepturus</i> Acts as A Highly Immunogen in BALB/c Mice Against the Lethality of Scorpion Venom
title_short Novel Mutant Phospholipase D from <i>Hemiscorpius lepturus</i> Acts as A Highly Immunogen in BALB/c Mice Against the Lethality of Scorpion Venom
title_sort novel mutant phospholipase d from i hemiscorpius lepturus i acts as a highly immunogen in balb c mice against the lethality of scorpion venom
topic <i>Hemiscorpius lepturus (H. lepturus)</i>
phospholipase D (PLD)
Freund’s adjuvant
alum adjuvant
dermonecrosis
vaccine
url https://www.mdpi.com/1420-3049/25/7/1673
work_keys_str_mv AT abouzarsoleimanimoez novelmutantphospholipasedfromihemiscorpiuslepturusiactsasahighlyimmunogeninbalbcmiceagainstthelethalityofscorpionvenom
AT rezahsajedi novelmutantphospholipasedfromihemiscorpiuslepturusiactsasahighlyimmunogeninbalbcmiceagainstthelethalityofscorpionvenom
AT kamranpooshangbagheri novelmutantphospholipasedfromihemiscorpiuslepturusiactsasahighlyimmunogeninbalbcmiceagainstthelethalityofscorpionvenom
AT jeanmarcsabatier novelmutantphospholipasedfromihemiscorpiuslepturusiactsasahighlyimmunogeninbalbcmiceagainstthelethalityofscorpionvenom
AT delavarshahbazzadeh novelmutantphospholipasedfromihemiscorpiuslepturusiactsasahighlyimmunogeninbalbcmiceagainstthelethalityofscorpionvenom