Epitope Mapping of Tetanus Toxin by Monoclonal Antibodies: Implication for Immunotherapy and Vaccine Design

Ghotloo, Somayeh; Golsaz‐Shirazi, Forough; Amiri, Mohammad Mehdi; Jeddi‐Tehrani, Mahmood; Shokri, Fazel

doi:10.1007/s12640-019-00096-w

Cited by 20 publications

(14 citation statements)

References 31 publications

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“…In the case of tetanus, recent research has focused on human monoclonal antibodies (humAbs) anti-TeNT (Wang et al 2016 , 2021 ; Aliprandini et al 2019 ; Ghotloo et al 2020 ; Minamitani et al 2021 ; Pirazzini et al 2021 ; Zhang et al 2021 ) with the aim of overcoming some clinical problems encountered with the use of the IgG fraction isolated from human polyclonal antisera derived from tetanus toxoid immunized donors (Pirazzini et al 2021 ). The toxin neutralizing humAbs were identified using phage display libraries or by screening antibody producing cells isolated from human individuals that were treated in adult age with the tetanus toxoid vaccine.…”

Section: Toxicology Of Tetanus and Botulinum Neurotoxinsmentioning

confidence: 99%

Toxicology and pharmacology of botulinum and tetanus neurotoxins: an update

2022

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Tetanus and botulinum neurotoxins cause the neuroparalytic syndromes of tetanus and botulism, respectively, by delivering inside different types of neurons, metalloproteases specifically cleaving the SNARE proteins that are essential for the release of neurotransmitters. Research on their mechanism of action is intensively carried out in order to devise improved therapies based on antibodies and chemical drugs. Recently, major results have been obtained with human monoclonal antibodies and with single chain antibodies that have allowed one to neutralize the metalloprotease activity of botulinum neurotoxin type A1 inside neurons. In addition, a method has been devised to induce a rapid molecular evolution of the metalloprotease domain of botulinum neurotoxin followed by selection driven to re-target the metalloprotease activity versus novel targets with respect to the SNARE proteins. At the same time, an intense and wide spectrum clinical research on novel therapeutics based on botulinum neurotoxins is carried out, which are also reviewed here.

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Section: Toxicology Of Tetanus and Botulinum Neurotoxinsmentioning

confidence: 99%

Toxicology and pharmacology of botulinum and tetanus neurotoxins: an update

2022

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“…Hence, TTFC has become a very interesting candidate from an immunological point of view, as it could protect against tetanus. Ghotloo et al [66] gathered the state of knowledge on epitope mapping of TT and, more particularly, the epitopes localized on the TTFC by mAbs.…”

Section: Immunological Properties Against Tetanusmentioning

confidence: 99%

Tetanus Toxin Fragment C: Structure, Drug Discovery Research and Production

et al. 2022

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Tetanus toxoid (TTd) plays an important role in the pharmaceutical world, especially in vaccines. The toxoid is obtained after formaldehyde treatment of the tetanus toxin. In parallel, current emphasis in the drug discovery field is put on producing well-defined and safer drugs, explaining the interest in finding new alternative proteins. The tetanus toxin fragment C (TTFC) has been extensively studied both as a neuroprotective agent for central nervous system disorders owing to its neuronal properties and as a carrier protein in vaccines. Indeed, it is derived from a part of the tetanus toxin and, as such, retains its immunogenic properties without being toxic. Moreover, this fragment has been well characterized, and its entire structure is known. Here, we propose a systematic review of TTFC by providing information about its structural features, its properties and its methods of production. We also describe the large uses of TTFC in the field of drug discovery. TTFC can therefore be considered as an attractive alternative to TTd and remarkably offers a wide range of uses, including as a carrier, delivery vector, conjugate, booster, inducer, and neuroprotector.

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“…Several TeNT-neutralizing human antibodies have been reported 7 – 11 , but it is still relatively unclear which targeted TeNT domains are required for these antibodies’ neutralization activity. In addition, it has been reported that combinations of different antibodies, such as TIG, lead to enhanced neutralizing activity 9 , but it is not well understood which antibodies in such mixtures contribute to neutralization. To address these questions we isolated TeNT-reactive human antibody clones and assessed their TeNT inhibitory activity.…”

Section: Introductionmentioning

confidence: 99%

Novel neutralizing human monoclonal antibodies against tetanus neurotoxin

Minamitani

Kiyose

Otsubo

et al. 2021

Sci Rep

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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.

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Epitope Mapping of Tetanus Toxin by Monoclonal Antibodies: Implication for Immunotherapy and Vaccine Design

Cited by 20 publications

References 31 publications

Toxicology and pharmacology of botulinum and tetanus neurotoxins: an update

Toxicology and pharmacology of botulinum and tetanus neurotoxins: an update

Tetanus Toxin Fragment C: Structure, Drug Discovery Research and Production

Novel neutralizing human monoclonal antibodies against tetanus neurotoxin

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