A Combined Strategy to Improve the Development of a Coral Antivenom Against Micrurus spp.
Accidents involving Micrurus snakes are not the most common ones but are noteworthy due to their severity. Victims envenomed by Micrurus snakes are at high risk of death and therefore must be treated with coral antivenom. In Brazil, the immunization mixture used to fabricate coral antivenom contains...
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doaj-13afa8fb671d418e81059cc93d485b452020-11-25T01:28:39ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-10-011010.3389/fimmu.2019.02422474940A Combined Strategy to Improve the Development of a Coral Antivenom Against Micrurus spp.Karen Larissa Pereira de Castro0Letícia Lopes-de-Souza1Daysiane de Oliveira2Ricardo Andrez Machado-de-Ávila3Ana Luiza Bittencourt Paiva4Cláudio F. de Freitas5Paulo Lee Ho6Carlos Chávez-Olórtegui7Clara Guerra-Duarte8Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, United StatesDepartamento de Bioquímica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilUniversidade de Extremo Sul Catarinense, Criciúma, BrazilUniversidade de Extremo Sul Catarinense, Criciúma, BrazilFundação Ezequiel Dias, Belo Horizonte, BrazilFundação Ezequiel Dias, Belo Horizonte, BrazilInstituto Butantan, São Paulo, BrazilDepartamento de Bioquímica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilFundação Ezequiel Dias, Belo Horizonte, BrazilAccidents involving Micrurus snakes are not the most common ones but are noteworthy due to their severity. Victims envenomed by Micrurus snakes are at high risk of death and therefore must be treated with coral antivenom. In Brazil, the immunization mixture used to fabricate coral antivenom contains Micrurus frontalis and Micrurus corallinus venoms, which are difficult to be obtained in adequate amounts. Different approaches to solve the venom limitation problem have been attempted, including the use of synthetic and recombinant antigens as substitutes. The present work proposes a combined immunization protocol, using priming doses of M. frontalis venom and booster doses of synthetic B-cell epitopes derived from M. corallinus toxins (four three-finger toxins-3FTX; and one phospholipase A2-PLA2) to obtain coral antivenom in a rabbit model. Immunized animals elicited a humoral response against both M. frontalis and M. corallinus venoms, as detected by sera reactivity in ELISA and Western Blot. Relevant cross-reactivity of the obtained sera with other Micrurus species (Micrurus altirostris, Micrurus lemniscatus, Micrurus spixii, Micrurus surinamensis) venoms was also observed. The elicited antibodies were able to neutralize PLA2 activity of both M. frontalis and M. corallinus venoms. In vivo, immunized rabbit sera completely protected mice from a challenge with 1.5 median lethal dose (LD50) of M. corallinus venom and 50% of mice challenged with 1.5 LD50 of M. frontalis venom. These results show that this combined protocol may be a suitable alternative to reduce the amount of venom used in coral antivenom production in Brazil.https://www.frontiersin.org/article/10.3389/fimmu.2019.02422/fullantivenomsynthetic peptidesMicrurussnakeepitopesthree-finger toxins |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Karen Larissa Pereira de Castro Letícia Lopes-de-Souza Daysiane de Oliveira Ricardo Andrez Machado-de-Ávila Ana Luiza Bittencourt Paiva Cláudio F. de Freitas Paulo Lee Ho Carlos Chávez-Olórtegui Clara Guerra-Duarte |
spellingShingle |
Karen Larissa Pereira de Castro Letícia Lopes-de-Souza Daysiane de Oliveira Ricardo Andrez Machado-de-Ávila Ana Luiza Bittencourt Paiva Cláudio F. de Freitas Paulo Lee Ho Carlos Chávez-Olórtegui Clara Guerra-Duarte A Combined Strategy to Improve the Development of a Coral Antivenom Against Micrurus spp. Frontiers in Immunology antivenom synthetic peptides Micrurus snake epitopes three-finger toxins |
author_facet |
Karen Larissa Pereira de Castro Letícia Lopes-de-Souza Daysiane de Oliveira Ricardo Andrez Machado-de-Ávila Ana Luiza Bittencourt Paiva Cláudio F. de Freitas Paulo Lee Ho Carlos Chávez-Olórtegui Clara Guerra-Duarte |
author_sort |
Karen Larissa Pereira de Castro |
title |
A Combined Strategy to Improve the Development of a Coral Antivenom Against Micrurus spp. |
title_short |
A Combined Strategy to Improve the Development of a Coral Antivenom Against Micrurus spp. |
title_full |
A Combined Strategy to Improve the Development of a Coral Antivenom Against Micrurus spp. |
title_fullStr |
A Combined Strategy to Improve the Development of a Coral Antivenom Against Micrurus spp. |
title_full_unstemmed |
A Combined Strategy to Improve the Development of a Coral Antivenom Against Micrurus spp. |
title_sort |
combined strategy to improve the development of a coral antivenom against micrurus spp. |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-10-01 |
description |
Accidents involving Micrurus snakes are not the most common ones but are noteworthy due to their severity. Victims envenomed by Micrurus snakes are at high risk of death and therefore must be treated with coral antivenom. In Brazil, the immunization mixture used to fabricate coral antivenom contains Micrurus frontalis and Micrurus corallinus venoms, which are difficult to be obtained in adequate amounts. Different approaches to solve the venom limitation problem have been attempted, including the use of synthetic and recombinant antigens as substitutes. The present work proposes a combined immunization protocol, using priming doses of M. frontalis venom and booster doses of synthetic B-cell epitopes derived from M. corallinus toxins (four three-finger toxins-3FTX; and one phospholipase A2-PLA2) to obtain coral antivenom in a rabbit model. Immunized animals elicited a humoral response against both M. frontalis and M. corallinus venoms, as detected by sera reactivity in ELISA and Western Blot. Relevant cross-reactivity of the obtained sera with other Micrurus species (Micrurus altirostris, Micrurus lemniscatus, Micrurus spixii, Micrurus surinamensis) venoms was also observed. The elicited antibodies were able to neutralize PLA2 activity of both M. frontalis and M. corallinus venoms. In vivo, immunized rabbit sera completely protected mice from a challenge with 1.5 median lethal dose (LD50) of M. corallinus venom and 50% of mice challenged with 1.5 LD50 of M. frontalis venom. These results show that this combined protocol may be a suitable alternative to reduce the amount of venom used in coral antivenom production in Brazil. |
topic |
antivenom synthetic peptides Micrurus snake epitopes three-finger toxins |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.02422/full |
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