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Recombinant antibodies against Iranian cobra venom as a new emerging therapy by phage display technology

BACKGROUND: The production of antivenom from immunized animals is an established treatment for snakebites; however, antibody phage display technology may have the capacity to delivery results more quickly and with a better match to local need. Naja oxiana, the Iranian cobra, is a medically important...

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Autores principales: Nazari, Ali, Samianifard, Maedeh, Rabie, Hadi, Mirakabadi, Abbas Zare
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Centro de Estudos de Venenos e Animais Peçonhentos 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346683/
https://www.ncbi.nlm.nih.gov/pubmed/32695146
http://dx.doi.org/10.1590/1678-9199-JVATITD-2019-0099
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author Nazari, Ali
Samianifard, Maedeh
Rabie, Hadi
Mirakabadi, Abbas Zare
author_facet Nazari, Ali
Samianifard, Maedeh
Rabie, Hadi
Mirakabadi, Abbas Zare
author_sort Nazari, Ali
collection PubMed
description BACKGROUND: The production of antivenom from immunized animals is an established treatment for snakebites; however, antibody phage display technology may have the capacity to delivery results more quickly and with a better match to local need. Naja oxiana, the Iranian cobra, is a medically important species, responsible for a significant number of deaths annually. This study was designed as proof of principle to determine whether recombinant antibodies with the capacity to neutralize cobra venom could be isolated by phage display. METHODS: Toxic fractions from cobra venom were prepared by chromatography and used as targets in phage display to isolate recombinant antibodies from a human scFv library. Candidate antibodies were expressed in E. coli HB2151 and purified by IMAC chromatography. The selected clones were analyzed in in vivo and in vitro experiments. RESULTS: Venom toxicity was contained in two fractions. Around a hundred phage clones were isolated against each fraction, those showing the best promise were G12F3 and G1F4. While all chosen clones showed low but detectable neutralizing effect against Naja oxiana venom, clone G12F3 could inhibit PLA(2) activity. CONCLUSION: Therefore, phage display is believed to have a good potential as an approach to the development of snake antivenom.
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spelling pubmed-73466832020-07-20 Recombinant antibodies against Iranian cobra venom as a new emerging therapy by phage display technology Nazari, Ali Samianifard, Maedeh Rabie, Hadi Mirakabadi, Abbas Zare J Venom Anim Toxins Incl Trop Dis Research BACKGROUND: The production of antivenom from immunized animals is an established treatment for snakebites; however, antibody phage display technology may have the capacity to delivery results more quickly and with a better match to local need. Naja oxiana, the Iranian cobra, is a medically important species, responsible for a significant number of deaths annually. This study was designed as proof of principle to determine whether recombinant antibodies with the capacity to neutralize cobra venom could be isolated by phage display. METHODS: Toxic fractions from cobra venom were prepared by chromatography and used as targets in phage display to isolate recombinant antibodies from a human scFv library. Candidate antibodies were expressed in E. coli HB2151 and purified by IMAC chromatography. The selected clones were analyzed in in vivo and in vitro experiments. RESULTS: Venom toxicity was contained in two fractions. Around a hundred phage clones were isolated against each fraction, those showing the best promise were G12F3 and G1F4. While all chosen clones showed low but detectable neutralizing effect against Naja oxiana venom, clone G12F3 could inhibit PLA(2) activity. CONCLUSION: Therefore, phage display is believed to have a good potential as an approach to the development of snake antivenom. Centro de Estudos de Venenos e Animais Peçonhentos 2020-06-19 /pmc/articles/PMC7346683/ /pubmed/32695146 http://dx.doi.org/10.1590/1678-9199-JVATITD-2019-0099 Text en https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License
spellingShingle Research
Nazari, Ali
Samianifard, Maedeh
Rabie, Hadi
Mirakabadi, Abbas Zare
Recombinant antibodies against Iranian cobra venom as a new emerging therapy by phage display technology
title Recombinant antibodies against Iranian cobra venom as a new emerging therapy by phage display technology
title_full Recombinant antibodies against Iranian cobra venom as a new emerging therapy by phage display technology
title_fullStr Recombinant antibodies against Iranian cobra venom as a new emerging therapy by phage display technology
title_full_unstemmed Recombinant antibodies against Iranian cobra venom as a new emerging therapy by phage display technology
title_short Recombinant antibodies against Iranian cobra venom as a new emerging therapy by phage display technology
title_sort recombinant antibodies against iranian cobra venom as a new emerging therapy by phage display technology
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346683/
https://www.ncbi.nlm.nih.gov/pubmed/32695146
http://dx.doi.org/10.1590/1678-9199-JVATITD-2019-0099
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