Immunologic and Protective Properties of Subunit- vs. Whole Toxoid-Derived Anti-Botulinum Equine Antitoxin.
Abstract: Botulism is a paralytic disease caused by botulinum neurotoxins (BoNTs). Equine antitoxin is currently the standard therapy for botulism in human. The preparation of equine antitoxin relies on the immunization of horses with botulinum toxoid, which suffers from low yield and safety limitations. The Hc fragment of BoNTs was suggested to be a potent antibotulinum subunit vaccine. The current study presents a comparative evaluation of equine-based toxoid-derived antitoxin (TDA) and subunit-derived antitoxin (SDA). The potency of recombinant Hc/A, Hc/B, and Hc/E in mice was similar to that of toxoids of the corresponding serotypes. A single boost with Hc/E administered to a toxoid E-hyperimmune horse increased the neutralizing antibody concentration (NAC) from 250 to 850 IU/mL. Immunization of naïve horses with the recombinant subunits induced a NAC comparable to that of horses immunized with the toxoid. SDA and TDA bound common epitopes on BoNTs, as demonstrated by an in vitro competition binding assay. In vivo, SDA and TDA showed similar efficacy when administered to guinea pigs postexposure to a lethal dose of botulinum toxins. Collectively, the results of the current study suggest that recombinant BoNT subunits may replace botulinum toxoids as efficient and safe antigens for the preparation of pharmaceutical anti-botulinum equine antitoxins.
Publication Date: 2022-09-14 PubMed ID: 36146601PubMed Central: PMC9506527DOI: 10.3390/vaccines10091522Google Scholar: Lookup
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- Journal Article
Summary
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The research article focuses on comparing the effectiveness of botulism treatments derived from whole toxoids and subunits, specifically examining equine antitoxin. The results suggest that recombinant botulinum neurotoxin (BoNT) subunits could potentially replace current botulinum toxoids in creating these equine antitoxins, providing a safer and more efficient treatment.
Overview of the Research
- Botulism is a dangerous illness caused by botulinum neurotoxins (BoNTs). The standard treatment currently involves the use of equine antitoxin, which is prepared by immunizing horses with a botulinum toxoid. However, this method has safety risks and yields low amounts of the antitoxin.
- This study explored the use of the Hc fragment of BoNTs as a potential antibotulinum subunit vaccine, aiming to evaluate the comparative effectiveness of toxoid-derived (TDA) and subunit-derived (SDA) antitoxins.
Findings on Subunit vs. Whole Toxoid-Derived Equine Antitoxins
- Researchers conducted tests on mice using recombinant Hc/A, Hc/B, and Hc/E, finding that the potency of these was similar to that of the corresponding serotype toxoids. This indicates that the subunits can be just as effective as the whole toxin.
- Administering a single boost of Hc/E to a horse hyperimmune to toxoid E significantly increased the neutralizing antibody concentration (NAC), indicating that the subunits can effectively boost immunity.
- Horses which were immunized with the recombinant subunits displayed a NAC comparable to those horses immunized with the toxoid. This further suggests that subunit vaccines can be just as efficient as toxoid ones in inducing an immune response.
- An in vitro competition binding assay showed that both the SDA and TDA bound common epitopes on BoNTs.
- When guinea pigs were exposed to lethal doses of botulinum toxins and were given treatment, SDA and TDA showed similar efficacy.
Implications of the Research
- The study suggests that using recombinant BoNT subunits could be a safer and more efficient way to prepare pharmaceutical anti-botulinum equine antitoxins, possibly eliminating the need for the traditional, less efficient botulinum toxoids.
- This potential new treatment method could be key in battling botulism, given the paralyzing and potentially lethal nature of the disease.
Cite This Article
APA
Ben David A, Barnea A, Torgeman A, Diamant E, Dor E, Schwartz A, Rosen O, Caspi N, Saraf M, Lerer E, Adar Y, Lupo E, Toister E, Zichel R.
(2022).
Immunologic and Protective Properties of Subunit- vs. Whole Toxoid-Derived Anti-Botulinum Equine Antitoxin.
Vaccines (Basel), 10(9), 1522.
https://doi.org/10.3390/vaccines10091522 Publication
Researcher Affiliations
- Department of Biotechnology, Israel Institute for Biological Research, Ness-Ziona 7410001, Israel.
- Department of Biotechnology, Israel Institute for Biological Research, Ness-Ziona 7410001, Israel.
- Department of Biotechnology, Israel Institute for Biological Research, Ness-Ziona 7410001, Israel.
- Department of Biotechnology, Israel Institute for Biological Research, Ness-Ziona 7410001, Israel.
- Department of Biotechnology, Israel Institute for Biological Research, Ness-Ziona 7410001, Israel.
- Department of Biotechnology, Israel Institute for Biological Research, Ness-Ziona 7410001, Israel.
- Department of Biotechnology, Israel Institute for Biological Research, Ness-Ziona 7410001, Israel.
- Veterinary Center for Preclinical Research, Israel Institute for Biological Research, Ness-Ziona 7410001, Israel.
- Veterinary Center for Preclinical Research, Israel Institute for Biological Research, Ness-Ziona 7410001, Israel.
- Department of Biotechnology, Israel Institute for Biological Research, Ness-Ziona 7410001, Israel.
- Department of Biotechnology, Israel Institute for Biological Research, Ness-Ziona 7410001, Israel.
- Department of Biotechnology, Israel Institute for Biological Research, Ness-Ziona 7410001, Israel.
- Department of Biotechnology, Israel Institute for Biological Research, Ness-Ziona 7410001, Israel.
- Department of Biotechnology, Israel Institute for Biological Research, Ness-Ziona 7410001, Israel.
Grant Funding
- SB-156 / Israel Institute for Biological Research
Conflict of Interest Statement
The authors declare no conflict of interest.
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