Tetanus Neurotoxin Neutralizing Antibodies Screened from a Human Immune scFv Antibody Phage Display Library
Tetanus neurotoxin (TeNT) produced by Clostridium tetani is one of the most poisonous protein substances. Neutralizing antibodies against TeNT can effectively prevent and cure toxicosis. Using purified Hc fragments of TeNT (TeNT-Hc) as an antigen, three specific neutralizing antibody clones recogniz...
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doaj-a3a88c09117d49e08f08c9d57f61fb502020-11-24T23:31:18ZengMDPI AGToxins2072-66512016-09-018926610.3390/toxins8090266toxins8090266Tetanus Neurotoxin Neutralizing Antibodies Screened from a Human Immune scFv Antibody Phage Display LibraryHan Wang0Rui Yu1Ting Fang2Ting Yu3Xiangyang Chi4Xiaopeng Zhang5Shuling Liu6Ling Fu7Changming Yu8Wei Chen9Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, ChinaTetanus neurotoxin (TeNT) produced by Clostridium tetani is one of the most poisonous protein substances. Neutralizing antibodies against TeNT can effectively prevent and cure toxicosis. Using purified Hc fragments of TeNT (TeNT-Hc) as an antigen, three specific neutralizing antibody clones recognizing different epitopes were selected from a human immune scFv antibody phage display library. The three antibodies (2-7G, 2-2D, and S-4-7H) can effectively inhibit the binding between TeNT-Hc and differentiated PC-12 cells in vitro. Moreover, 2-7G inhibited TeNT-Hc binding to the receptor via carbohydrate-binding sites of the W pocket while 2-2D and S-4-7H inhibited binding of the R pocket. Although no single mAb completely protected mice from the toxin, they could both prolong survival when challenged with 20 LD50s (50% of the lethal dose) of TeNT. When used together, the mAbs completely neutralized 1000 LD50s/mg Ab, indicating their high neutralizing potency in vivo. Antibodies recognizing different carbohydrate-binding pockets could have higher synergistic toxin neutralization activities than those that recognize the same pockets. These results could lead to further production of neutralizing antibody drugs against TeNT and indicate that using TeNT-Hc as an antigen for screening human antibodies for TeNT intoxication therapy from human immune antibody library was convenient and effective.http://www.mdpi.com/2072-6651/8/9/266tetanus neurotoxinsHc fragmentneutralizing antibodyhuman immune scFv antibody phage display libraryphage display |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Han Wang Rui Yu Ting Fang Ting Yu Xiangyang Chi Xiaopeng Zhang Shuling Liu Ling Fu Changming Yu Wei Chen |
spellingShingle |
Han Wang Rui Yu Ting Fang Ting Yu Xiangyang Chi Xiaopeng Zhang Shuling Liu Ling Fu Changming Yu Wei Chen Tetanus Neurotoxin Neutralizing Antibodies Screened from a Human Immune scFv Antibody Phage Display Library Toxins tetanus neurotoxins Hc fragment neutralizing antibody human immune scFv antibody phage display library phage display |
author_facet |
Han Wang Rui Yu Ting Fang Ting Yu Xiangyang Chi Xiaopeng Zhang Shuling Liu Ling Fu Changming Yu Wei Chen |
author_sort |
Han Wang |
title |
Tetanus Neurotoxin Neutralizing Antibodies Screened from a Human Immune scFv Antibody Phage Display Library |
title_short |
Tetanus Neurotoxin Neutralizing Antibodies Screened from a Human Immune scFv Antibody Phage Display Library |
title_full |
Tetanus Neurotoxin Neutralizing Antibodies Screened from a Human Immune scFv Antibody Phage Display Library |
title_fullStr |
Tetanus Neurotoxin Neutralizing Antibodies Screened from a Human Immune scFv Antibody Phage Display Library |
title_full_unstemmed |
Tetanus Neurotoxin Neutralizing Antibodies Screened from a Human Immune scFv Antibody Phage Display Library |
title_sort |
tetanus neurotoxin neutralizing antibodies screened from a human immune scfv antibody phage display library |
publisher |
MDPI AG |
series |
Toxins |
issn |
2072-6651 |
publishDate |
2016-09-01 |
description |
Tetanus neurotoxin (TeNT) produced by Clostridium tetani is one of the most poisonous protein substances. Neutralizing antibodies against TeNT can effectively prevent and cure toxicosis. Using purified Hc fragments of TeNT (TeNT-Hc) as an antigen, three specific neutralizing antibody clones recognizing different epitopes were selected from a human immune scFv antibody phage display library. The three antibodies (2-7G, 2-2D, and S-4-7H) can effectively inhibit the binding between TeNT-Hc and differentiated PC-12 cells in vitro. Moreover, 2-7G inhibited TeNT-Hc binding to the receptor via carbohydrate-binding sites of the W pocket while 2-2D and S-4-7H inhibited binding of the R pocket. Although no single mAb completely protected mice from the toxin, they could both prolong survival when challenged with 20 LD50s (50% of the lethal dose) of TeNT. When used together, the mAbs completely neutralized 1000 LD50s/mg Ab, indicating their high neutralizing potency in vivo. Antibodies recognizing different carbohydrate-binding pockets could have higher synergistic toxin neutralization activities than those that recognize the same pockets. These results could lead to further production of neutralizing antibody drugs against TeNT and indicate that using TeNT-Hc as an antigen for screening human antibodies for TeNT intoxication therapy from human immune antibody library was convenient and effective. |
topic |
tetanus neurotoxins Hc fragment neutralizing antibody human immune scFv antibody phage display library phage display |
url |
http://www.mdpi.com/2072-6651/8/9/266 |
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