Engineered antigen containing epitopes from Loxosceles spp. spider toxins induces a monoclonal antibody (Lox-mAb3) against astacin-like metalloproteases

被引：8

作者：

Costa, Tamara G. F. ^{[1
,2
]}

Costal-Oliveira, Fernanda ^{[1
,2
]}

de Assis, Thamyres C. S. ^{[1
,2
]}

Lima, Sabrina A. ^{[1
,2
]}

Martins, Christina A. ^{[1
,2
]}

Finco, Alessandra B. ^{[3
]}

Veiga, Silvio S. ^{[3
]}

Soccol, Vanete T. ^{[3
]}

Machado-de-Avila, Ricardo A. ^{[4
]}

Figueiredo, Luis F. M. ^{[5
]}

Minozzo, Joao C. ^{[6
]}

Kalapothakis, Evanguedes ^{[1
,2
]}

Guerra-Duarte, Clara ^{[7
]}

Alvarenga, Larissa M. ^{[3
]}

Chavez-Olortegui, Carlos ^{[1
,2
]}

机构：

[1] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, Antonio Carlos 6627, Belo Horizonte, MG, Brazil

[2] Univ Fed Minas Gerais, Inst Ciencias Biol, Genet Ecol & Evolucao, Belo Horizonte, MG, Brazil

[3] Univ Fed Parana UFPR, Curitiba, PR, Brazil

[4] Univ Extremo Sul Catarinense UNESC, Criciuma, SC, Brazil

[5] Univ Tecnol Fed Parana UTFPR, Toledo, PR, Brazil

[6] Ctr Pesquisa & Prod Imunobiol CPPI, Curitiba, PR, Brazil

[7] Fundacao Ezequiel Dias, Ctr Pesquisa Desenvolvimento, BR-30510010 Belo Horizonte, MG, Brazil

来源：

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES | 2020年 / 162卷

关键词：

Monoclonal antibodies; Metalloprotease; Loxosceles spider venoms; Multiepitopic recombinant protein; FUNCTIONAL-CHARACTERIZATION; SPHINGOMYELINASES-D; VENOM; IDENTIFICATION; GENERATION; PROTECTION; EXPRESSION; ANTIVENOM; CLONING;

D O I：

10.1016/j.ijbiomac.2020.06.176

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Loxoscelism pose a health issue in the South America. The treatment for these accidents is based on the administration of antivenom produced in animals immunized with Loxosceles venom. In this work, a previously produced non-toxic multiepitopic chimeric protein (rMEPlox), composed of epitopes derived from the main toxins families (sphyngomielinase-D, metalloproteases, and hyaluronidases) of Loxosceles spider venoms, was used as antigen to produce monoclonal antibodies (mAbs). A selected anti-rMEPlox mAb (Lox-mAb3) reacted with metalloprotease from L. intermedia venom and showed cross-reactivity with metalloproteses from Brazilian and Peruvian Loxosceles laeta and Loxosceles gaucho venoms in immunoassays. The sequence recognized by Lox-mAb3 ((184)ENNTRTIGPFDYDSIMLYGAY(205)) corresponds to the C-terminal region of Astacin-like metalloprotease 1 and the amino acid sequence IGPFDYDSI, conserved among the homologs metalloproteases sequences, is important for antibody recognition. Lox-mAb3 neutralizes the fibrinogenolytic activity caused by metalloprotease from L. intermedia spider venom in vitro, which may lead to a decrease in hemorrhagic disturbances caused by Loxosceles envenomation. Our results show, for the first time, the use of a non-toxic multiepitopic protein for the production of a neutralizing monoclonal antibody against a metalloprotease of medically important Loxosceles venoms. These results contribute for the production improvement of therapeutic antivenom against loxoscelism. (c) 2020 Elsevier B.V. All rights reserved.

引用

页码：490 / 500

页数：11