A conserved sequence region of scorpion toxins rendered immunogenic induces broadly cross-reactive, neutralizing antibodies.
Scorpion toxins constitute a family of proteins with a high degree of sequence diversity but a common mode of action. Neutralization of the toxic effects of scorpion stings by serotherapy is limited due to the various serotypes expressed by these proteins. We explored the possibility of raising antibodies to conserved parts of the toxins which could recognize several members of the family. We established the variability profile of a set of 25 scorpion toxin sequences, then evaluated systematically by peptide-scanning methods the antigenicity of one scorpion toxin. The most conserved regions were generally very poorly antigenic. One exception was the N-terminal region, which is both conserved and antigenic. Antibodies were raised in rabbits against an eight-residue synthetic peptide mimicking the N-terminal region. These peptide antibodies were cross-reactive with several scorpion toxins belonging to different serotypes and neutralized both the pharmacological effects (binding to rat brain synaptosomes) and the biological activity (toxicity in mice) of the parent toxin. The molecular model of the toxin indicates that antibody binding to residues 1-8 probably either masks some residue(s) of the N-terminus critical for the biological activity or overlaps with the epitope previously defined by neutralizing monoclonal antibody. These findings could open the way for new therapeutic strategies for the medical care of envenomations.
Devaux
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C
CNRS URA 1455, Laboratoire de Biochimie, IFR Jean Roche, Faculté de Médecine Nord, Marseille, France.
Fourquet
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P
Granier
C
C
D000595:Amino Acid Sequence; D000818:Animals; D000937:Antigen-Antibody Reactions; D000992:Antitoxins / Q000737:chemistry*; D003429:Cross Reactions; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D017434:Protein Structure, Tertiary; D011817:Rabbits; D012604:Scorpion Venoms / Q000737:chemistry / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
D000992:Antitoxins; D010455:Peptides; D012604:Scorpion Venoms