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Research Article
Teruhito Yasui
Laboratory of Infectious Diseases and Immunity, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN)
Corresponding Author
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This work is licensed under a CC BY 4.0 License. Read Full License
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 Hn-reactive clones protected strongly against TeNT toxicity in mice. Furthermore, combination treatment of Hn-reactive antibody clones with both Hc-reactive and TeNT mix–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.
Keywords
Tetanus, tetanus neurotoxin (TeNT), antibodies, immunology
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CURRENT STATUS: Under Review
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Posted 17 Mar, 2021
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Review #1 received
Received 10 Apr, 2021
Review #2 received
Received 10 Apr, 2021
Review #3 received
Received 10 Apr, 2021
Review #4 received
Received 10 Apr, 2021
Reviewer #8 agreed
On 06 Apr, 2021
Reviewer #9 agreed
On 05 Apr, 2021
Reviewer #11 agreed
On 05 Apr, 2021
Reviewer #5 agreed
On 05 Apr, 2021
Reviewer #12 agreed
On 05 Apr, 2021
Reviewer #6 agreed
On 05 Apr, 2021
Reviewer #4 agreed
On 05 Apr, 2021
Reviewer #7 agreed
On 05 Apr, 2021
Reviewer #10 agreed
On 05 Apr, 2021
Reviewer #17 agreed
On 31 Mar, 2021
Reviewer #31 agreed
On 31 Mar, 2021
Reviewer #14 agreed
On 31 Mar, 2021
Reviewer #2 agreed
On 31 Mar, 2021
Reviewer #37 agreed
On 31 Mar, 2021
Reviewer #29 agreed
On 31 Mar, 2021
Reviewer #39 agreed
On 31 Mar, 2021
Reviewer #1 agreed
On 31 Mar, 2021
Reviewer #33 agreed
On 31 Mar, 2021
Reviewer #40 agreed
On 31 Mar, 2021
Reviewer #30 agreed
On 31 Mar, 2021
Reviewer #41 agreed
On 31 Mar, 2021
Reviewer #28 agreed
On 31 Mar, 2021
Reviewer #3 agreed
On 31 Mar, 2021
Reviewer #16 agreed
On 31 Mar, 2021
Reviewer #34 agreed
On 31 Mar, 2021
Reviewer #42 agreed
On 31 Mar, 2021
Reviewer #32 agreed
On 31 Mar, 2021
Reviewer #35 agreed
On 31 Mar, 2021
Reviewer #38 agreed
On 31 Mar, 2021
Reviewer #15 agreed
On 31 Mar, 2021
Reviewer #13 agreed
On 31 Mar, 2021
Reviewers invited
Invitations sent on 30 Mar, 2021
Editor assigned
On 30 Mar, 2021
Editor invited
On 16 Mar, 2021
Submission checks complete
On 16 Mar, 2021
First submitted
On 02 Mar, 2021
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Subject Areas
Immunology
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This preprint is under consideration at Scientific Reports. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Teruhito Yasui
Laboratory of Infectious Diseases and Immunity, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN)
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 17 Mar, 2021
No community comments so far
Review #1 received
Received 10 Apr, 2021
Review #2 received
Received 10 Apr, 2021
Review #3 received
Received 10 Apr, 2021
Review #4 received
Received 10 Apr, 2021
Reviewer #8 agreed
On 06 Apr, 2021
Reviewer #9 agreed
On 05 Apr, 2021
Reviewer #11 agreed
On 05 Apr, 2021
Reviewer #5 agreed
On 05 Apr, 2021
Reviewer #12 agreed
On 05 Apr, 2021
Reviewer #6 agreed
On 05 Apr, 2021
Reviewer #4 agreed
On 05 Apr, 2021
Reviewer #7 agreed
On 05 Apr, 2021
Reviewer #10 agreed
On 05 Apr, 2021
Reviewer #17 agreed
On 31 Mar, 2021
Reviewer #31 agreed
On 31 Mar, 2021
Reviewer #14 agreed
On 31 Mar, 2021
Reviewer #2 agreed
On 31 Mar, 2021
Reviewer #37 agreed
On 31 Mar, 2021
Reviewer #29 agreed
On 31 Mar, 2021
Reviewer #39 agreed
On 31 Mar, 2021
Reviewer #1 agreed
On 31 Mar, 2021
Reviewer #33 agreed
On 31 Mar, 2021
Reviewer #40 agreed
On 31 Mar, 2021
Reviewer #30 agreed
On 31 Mar, 2021
Reviewer #41 agreed
On 31 Mar, 2021
Reviewer #28 agreed
On 31 Mar, 2021
Reviewer #3 agreed
On 31 Mar, 2021
Reviewer #16 agreed
On 31 Mar, 2021
Reviewer #34 agreed
On 31 Mar, 2021
Reviewer #42 agreed
On 31 Mar, 2021
Reviewer #32 agreed
On 31 Mar, 2021
Reviewer #35 agreed
On 31 Mar, 2021
Reviewer #38 agreed
On 31 Mar, 2021
Reviewer #15 agreed
On 31 Mar, 2021
Reviewer #13 agreed
On 31 Mar, 2021
Reviewers invited
Invitations sent on 30 Mar, 2021
Editor assigned
On 30 Mar, 2021
Editor invited
On 16 Mar, 2021
Submission checks complete
On 16 Mar, 2021
First submitted
On 02 Mar, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Immunology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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 Hn-reactive clones protected strongly against TeNT toxicity in mice. Furthermore, combination treatment of Hn-reactive antibody clones with both Hc-reactive and TeNT mix–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.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
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