title: An in vivo protective response against toxic effects of the dermonecrotic protein from Loxosceles intermedia spider venom elicited by synthetic epitopes.
abstract: Loxoscelism is a necrotic-hemolytic syndrome caused by bites of brown spiders belonging to the genus Loxosceles. Many approaches for the treatment of Loxosceles poisoning have already been proposed, among which administration of specific antivenom is thought to be the more specific. We have evaluated the use of peptides as immunogen to raise in rabbits an antibody response that could protect animals from a challenge by the Loxtox isoform LiD1, one of the main toxic component of Loxosceles intermedia venom. Six antigenic regions of LiD1 were mapped by using the SPOT method. The corresponding peptides were further chemically synthesized, mixed, and used as immunogens in rabbits. Control animal received recombinant LiD1 alone or together with peptides. We found that the rabbit antibody response to peptides was cross-reactive with LiD1, although only one peptide from the mix of six was immunogenic. The dermonecrotic, hemorrhagic and oedema forming activities induced by LiD1 in naïve rabbits were inhibited by 82%, 35% and 35% respectively, by preincubation of LiD1 with anti-peptide antibodies prepared from immunized rabbits. Animals that were immunized with peptides or LiD1r, were found to be protected from the dermonecrotic, hemorrhagic and oedema forming activities induced by a challenge with LiD1. The protection conferred by peptides was, however, lower than that provided by the peptide protein combination or by the full-length protein. These results encourage us in the utilization of synthetic peptides for therapeutic serum development or vaccination approaches.
authors.affiliation: Departamento de Bioquímica-Imunologia, ICB, Universidade Federal de Minas Gerais, Brazil. liza.felicori@sysdiag.cnrs.fr
authors.forename: Liza
authors.initials: L
authors.lastname: Felicori
authors.forename: Paula B
authors.initials: PB
authors.lastname: Fernandes
authors.forename: Mario S
authors.initials: MS
authors.lastname: Giusta
authors.forename: Clara G
authors.initials: CG
authors.lastname: Duarte
authors.forename: Evanguedes
authors.initials: E
authors.lastname: Kalapothakis
authors.forename: Christophe
authors.initials: C
authors.lastname: Nguyen
authors.forename: Frank
authors.initials: F
authors.lastname: Molina
authors.forename: Claude
authors.initials: C
authors.lastname: Granier
authors.forename: Carlos
authors.initials: C
authors.lastname: Chávez-Olórtegui
mesh_terms: D000818:Animals; D004487:Edema / Q000517:prevention & control; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006470:Hemorrhage / Q000517:prevention & control; D007299:Insect Bites and Stings / Q000276:immunology*; D009336:Necrosis / Q000517:prevention & control; D010727:Phosphoric Diester Hydrolases / Q000276:immunology*; D011817:Rabbits; D013111:Spider Venoms / Q000037:antagonists & inhibitors* / Q000276:immunology*; D013112:Spiders; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000939:Epitopes; D013111:Spider Venoms; D014614:Vaccines, Synthetic; C055161:loxosceles venom; D010727:Phosphoric Diester Hydrolases