Novel neutralizing human monoclonal antibodies against tetanus neurotoxin

Abstract Tetanus is a fatal disease caused by tetanus neurotoxin (TeNT). TeNT is composed of a light chain (Lc) and a heavy chain, the latter of which is classified into two domains, N-terminus Hn and C-terminus Hc. Several TeNT-neutralizing antibodies have been reported, but it remains unclear whic...

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Autores principales:	Takeharu Minamitani, Karin Kiyose, Ryota Otsubo, Toshihiro Ito, Hiroki Akiba, Rika A. Furuta, Tsuyoshi Inoue, Kouhei Tsumoto, Masahiro Satake, Teruhito Yasui
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/08bdd9b42c2f4314801819b5bb345170
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spelling	oai:doaj.org-article:08bdd9b42c2f4314801819b5bb3451702021-12-02T14:58:14ZNovel neutralizing human monoclonal antibodies against tetanus neurotoxin10.1038/s41598-021-91597-22045-2322https://doaj.org/article/08bdd9b42c2f4314801819b5bb3451702021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91597-2https://doaj.org/toc/2045-2322Abstract Tetanus is a fatal disease caused by tetanus neurotoxin (TeNT). TeNT is composed of a light chain (Lc) and a heavy chain, the latter of which is classified into two domains, N-terminus Hn and C-terminus Hc. Several TeNT-neutralizing antibodies have been reported, but it remains unclear which TeNT domains are involved in neutralization. To further understand the mechanism of these antibodies, we isolated TeNT-reactive human antibody clones from peripheral blood mononuclear cells. We then analyzed the reactivity of the isolated antibody clones to each protein domain and their inhibition of Hc-ganglioside GT1b binding, which is critical for TeNT toxicity. We also investigated the TeNT-neutralizing ability of isolated antibody clones and showed that an Hn-reactive clone protected strongly against TeNT toxicity in mice. Furthermore, combination treatment of Hn-reactive antibody clones with both Hc-reactive and TeNT mix (the mixture of Hc, Hn, and Lc proteins)–reactive antibody clones enhanced the neutralizing effect. These results indicated that antibody clones targeting Hn effectively neutralized TeNT. In addition, the use of a cocktail composed of Hc-, Hn-, and TeNT mix–reactive antibodies provided enhanced protection compared to the use of each antibody alone.Takeharu MinamitaniKarin KiyoseRyota OtsuboToshihiro ItoHiroki AkibaRika A. FurutaTsuyoshi InoueKouhei TsumotoMasahiro SatakeTeruhito YasuiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Takeharu Minamitani Karin Kiyose Ryota Otsubo Toshihiro Ito Hiroki Akiba Rika A. Furuta Tsuyoshi Inoue Kouhei Tsumoto Masahiro Satake Teruhito Yasui Novel neutralizing human monoclonal antibodies against tetanus neurotoxin
description	Abstract Tetanus is a fatal disease caused by tetanus neurotoxin (TeNT). TeNT is composed of a light chain (Lc) and a heavy chain, the latter of which is classified into two domains, N-terminus Hn and C-terminus Hc. Several TeNT-neutralizing antibodies have been reported, but it remains unclear which TeNT domains are involved in neutralization. To further understand the mechanism of these antibodies, we isolated TeNT-reactive human antibody clones from peripheral blood mononuclear cells. We then analyzed the reactivity of the isolated antibody clones to each protein domain and their inhibition of Hc-ganglioside GT1b binding, which is critical for TeNT toxicity. We also investigated the TeNT-neutralizing ability of isolated antibody clones and showed that an Hn-reactive clone protected strongly against TeNT toxicity in mice. Furthermore, combination treatment of Hn-reactive antibody clones with both Hc-reactive and TeNT mix (the mixture of Hc, Hn, and Lc proteins)–reactive antibody clones enhanced the neutralizing effect. These results indicated that antibody clones targeting Hn effectively neutralized TeNT. In addition, the use of a cocktail composed of Hc-, Hn-, and TeNT mix–reactive antibodies provided enhanced protection compared to the use of each antibody alone.
format	article
author	Takeharu Minamitani Karin Kiyose Ryota Otsubo Toshihiro Ito Hiroki Akiba Rika A. Furuta Tsuyoshi Inoue Kouhei Tsumoto Masahiro Satake Teruhito Yasui
author_facet	Takeharu Minamitani Karin Kiyose Ryota Otsubo Toshihiro Ito Hiroki Akiba Rika A. Furuta Tsuyoshi Inoue Kouhei Tsumoto Masahiro Satake Teruhito Yasui
author_sort	Takeharu Minamitani
title	Novel neutralizing human monoclonal antibodies against tetanus neurotoxin
title_short	Novel neutralizing human monoclonal antibodies against tetanus neurotoxin
title_full	Novel neutralizing human monoclonal antibodies against tetanus neurotoxin
title_fullStr	Novel neutralizing human monoclonal antibodies against tetanus neurotoxin
title_full_unstemmed	Novel neutralizing human monoclonal antibodies against tetanus neurotoxin
title_sort	novel neutralizing human monoclonal antibodies against tetanus neurotoxin
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/08bdd9b42c2f4314801819b5bb345170
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Novel neutralizing human monoclonal antibodies against tetanus neurotoxin

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