In vivo protection against Androctonus australis hector scorpion toxin and venom by immunization with a synthetic analog of toxin II.
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.
Zenouaki
I
I
Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, Tunisia.
Kharrat
R
R
Sabatier
J M
JM
Devaux
C
C
Karoui
H
H
Van Rietschoten
J
J
el Ayeb
M
M
Rochat
H
H
D000818:Animals; D000917:Antibody Formation; D000997:Antivenins / Q000737:chemistry / Q000276:immunology*; D005976:Glutaral / Q000276:immunology; D007928:Lethal Dose 50; D051379:Mice; D008810:Mice, Inbred C57BL; D009498:Neurotoxins / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology*; D011108:Polymers; D011817:Rabbits; D030162:Reptilian Proteins; D012604:Scorpion Venoms / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000276:immunology*
D000997:Antivenins; D009498:Neurotoxins; D011108:Polymers; D030162:Reptilian Proteins; D012604:Scorpion Venoms; D014614:Vaccines, Synthetic; C053969:scorpion toxin II, Androctonus; D005976:Glutaral