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Acta Trop. 2018 Jan;177:66-73. doi: 10.1016/j.actatropica.2017.09.001. Epub 2017 Sep 5.

Discovery of human scFvs that cross-neutralize the toxic effects of B. jararacussu and C. d. terrificus venoms.

Author information

1
Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
2
Health Sciences Center, Medical School, Federal University of Roraima, Boa Vista, RR, Brazil.
3
Department of Social Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
4
Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
5
Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: jebarbos@fmrp.usp.br.

Abstract

Accidents involving venomous snakes are a public health problem worldwide, causing a large number of deaths per year. In Brazil, the majority of accidents are caused by the Bothrops and Crotalus genera, which are responsible for approximately 80% of severe envenoming cases. The cross-neutralization of snake venoms by antibodies is an important issue for development of more effective treatments. Our group has previously reported the construction of human monoclonal antibody fragments towards Bothrops jararacussu and Crotalus durissus terrificus' venoms. This study aimed to select human single-chain variable fragments (scFvs) that recognize both bothropic and crotalic crude venoms following venoms neutralizing capacity in vitro and in vivo. The cross-reactivity of Cro-Bothrumabs were demonstrated by ELISA and in vitro and in vivo experiments showed that a combination of scFvs neutralizes in vitro toxic activities (e.g. indirect hemolysis and plasma-clotting) of crotalic and bothropic venoms as well as prolonged survival time of envenomed animals. Our results may contribute to the development of the first human polyvalent antivenom against Bothrops jararacussu and Crotalus durissus terrificus venoms, overcoming some undesirable effects caused by conventional serotherapy.

KEYWORDS:

Antivenom; Bothrops jararacussu; Crotalus durissus terrificus; Indirect hemolysis; Phage display; Plasma-clotting; scFv

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