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Toxins
Special Issues
Human Antibody Engineering for Prevention and Treatment of Botulism
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Human Antibody Engineering for Prevention and Treatment of Botulism

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Bacterial Toxins".

Deadline for manuscript submissions: closed (30 December 2023) | Viewed by 2099

Special Issue Editors

Dr. Shauna Farr-Jones

E-Mail Website
Guest Editor
Department of Anesthesia, University of California, San Francisco, CA, USA
Interests: recombinant antibodies; antibody drugs; antibody engineering
Dr. Milan T. Tomic

E-Mail Website
Guest Editor
Ology Bioservices, Subsidiary of National Resilience, Inc., Alameda, CA, USA
Interests: recombinant antibodies; antibody drug development; antibody manufacturing
Prof. Dr. James D. Marks

E-Mail Website
Guest Editor
Department of Anesthesia, University of California, San Francisco, CA, USA
Interests: antibody engineering; phage display; yeast display; recombinant antibodies; antibody drugs
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Botulinum neurotoxins have attracted the attention of researchers due to their extreme potency, unique mechanism of action, therapeutic applications, causation of the naturally occurring disease botulism and potential for misuse. While historically polyclonal antitoxins produced from immunized horses or humans have been used to treat botulism, engineered human antibodies produced from cell lines offer a number of significant advantages. The need for engineered human antitoxins has increasing urgency due to renewed concerns about the use of bioweapons and the aging of the existing equine antitoxin stockpile.

The purpose of this Special Issue of Toxins is to report on various antibody engineering efforts on next-generation botulinum antitoxins. The scope of this Special Issue includes the development and application of immunotherapy to treat and prevent botulism from multiple botulinum neurotoxin serotypes.

Dr. Shauna Farr-Jones
Dr. Milan T. Tomic
Prof. Dr. James D. Marks
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • botulinum antitoxin
  • recombinant antibodies
  • oligoclonal antibody products
  • human antibody drug products
  • antibody engineering

Published Papers (1 paper)

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Research

16 pages, 2106 KiB  
Article
A Three-Monoclonal Antibody Combination Potently Neutralizes BoNT/G Toxin in Mice
by Yongfeng Fan, Jianlong Lou, Christina C. Tam, Weihua Wen, Fraser Conrad, Priscila Leal da Silva Alves, Luisa W. Cheng, Consuelo Garcia-Rodriguez, Shauna Farr-Jones and James D. Marks
Toxins 2023, 15(5), 316; https://doi.org/10.3390/toxins15050316 - 30 Apr 2023
Cited by 2 | Viewed by 1677
Abstract
Equine-derived antitoxin (BAT®) is the only treatment for botulism from botulinum neurotoxin serotype G (BoNT/G). BAT® is a foreign protein with potentially severe adverse effects and is not renewable. To develop a safe, more potent, and renewable antitoxin, humanized monoclonal [...] Read more.
Equine-derived antitoxin (BAT®) is the only treatment for botulism from botulinum neurotoxin serotype G (BoNT/G). BAT® is a foreign protein with potentially severe adverse effects and is not renewable. To develop a safe, more potent, and renewable antitoxin, humanized monoclonal antibodies (mAbs) were generated. Yeast displayed single chain Fv (scFv) libraries were prepared from mice immunized with BoNT/G and BoNT/G domains and screened with BoNT/G using fluorescence-activated cell sorting (FACS). Fourteen scFv-binding BoNT/G were isolated with KD values ranging from 3.86 nM to 103 nM (median KD 20.9 nM). Five mAb-binding non-overlapping epitopes were humanized and affinity matured to create antibodies hu6G6.2, hu6G7.2, hu6G9.1, hu6G10, and hu6G11.2, with IgG KD values ranging from 51 pM to 8 pM. Three IgG combinations completely protected mice challenged with 10,000 LD50s of BoNT/G at a total mAb dose of 6.25 μg per mouse. The mAb combinations have the potential for use in the diagnosis and treatment of botulism due to serotype G and, along with antibody combinations to BoNT/A, B, C, D, E, and F, provide the basis for a fully recombinant heptavalent botulinum antitoxin to replace the legacy equine product. Full article
(This article belongs to the Special Issue Human Antibody Engineering for Prevention and Treatment of Botulism)
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