Human scFv antibodies (Afribumabs) against Africanized bee venom: Advances in melittin recognition

Autor(es)

Pessenda, Gabriela ^[1] ; Silva, Luciano C. ^[1] ; Campos, Lucas B. ^[1] ; Pacello, Elenice M. ^[1] ; Pucca, Manuela B. ^[2] ; Martinez, Edson Z. ^[3] ; Barbosa, Jose E. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Biochem & Immunol, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Chem & Phys, Ave Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Social Med, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Toxicon; v. 112, p. 59-67, MAR 15 2016.
• Citações Web of Science: 6

Resumo

Africanized Apis mellifera bees, also known as killer bees, have an exceptional defensive instinct, characterized by mass attacks that may cause envenomation or death. From the years 2000-2013, 77,066 bee accidents occurred in Brazil. Bee venom comprises several substances, including melittin and phospholipase A(2) (PLA(2)). Due to the lack of antivenom for bee envenomation, this study aimed to produce human monoclonal antibody fragments (single chain fragment variable; scFv), by using phage display technology. These fragments targeted melittin and PLA(2), the two major components of bee venom, to minimize their toxic effects in cases of mass envenomation. Two phage antibody selections were performed using purified melittin. As the commercial melittin is contaminated with PLA(2), phages specific to PLA(2) were also obtained during one of the selections. Specific clones for melittin and PLA(2) were selected for the production of soluble scFvs, named here Afribumabs: prefix: afrib- (from Africanized bee); stem/suffix:-umab (fully human antibody). Afribumabs 1 and 2 were tested in in vitro and in vivo assays to assess their ability to inhibit the toxic actions of purified melittin, PLA(2), and crude bee venom. Afribumabs reduced hemolysis caused by purified melittin and PLA(2) and by crude venom in vitro and reduced edema formation in the paws of mice and prolonged the survival of venom-injected animals in vivo. These results demonstrate that Afribumabs may contribute to the production of the first nonheterologous antivenom treatment against bee envenomation. Such a treatment may overcome some of the difficulties associated with conventional immunotherapy techniques. (C) 2016 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 12/12954-6 - Estudo das toxinas Ts6 e Ts15 do escorpião Tityus serrulatus como potenciais drogas terapêuticas para o tratamento de doenças autoimunes
• Beneficiário: Manuela Berto Pucca
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado