Therapeutic efficacy of equine botulism antitoxin in Rhesus macaques.
There are currently no licensed vaccines available for prevention of botulism in humans. The vaccination is not desirable due to expanding therapeutic indications of botulinum toxins. The only available specific treatment for botulism is antitoxin to remove circulating toxin, thus, preventing furthe...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5699824?pdf=render |
| _version_ | 1828751841401241600 |
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| author | Shantha Kodihalli Andrew Emanuel Teresa Takla Yi Hua Charles Hobbs Ross LeClaire Denise C O'Donnell |
| author_facet | Shantha Kodihalli Andrew Emanuel Teresa Takla Yi Hua Charles Hobbs Ross LeClaire Denise C O'Donnell |
| author_sort | Shantha Kodihalli |
| collection | DOAJ |
| description | There are currently no licensed vaccines available for prevention of botulism in humans. The vaccination is not desirable due to expanding therapeutic indications of botulinum toxins. The only available specific treatment for botulism is antitoxin to remove circulating toxin, thus, preventing further neuronal damage. BAT® (Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G)-(Equine)) has been developed and its therapeutic efficacy evaluated against botulinum neurotoxin serotype A (BoNT/A) in Rhesus macaques.In a post-exposure prophylaxis (PEP) study, animals were exposed to 4x LD50/kg of BoNT/A and administered intravenously with either BAT (1x or 0.1x scaled human dose), or placebo at 4 hours post-exposure. The animals were monitored for 14 days. For the therapeutic intervention studies, animals were exposed to a 1.7x LD50/kg of BoNT/A and treated intravenously with either placebo or BAT at a 1x scaled human dose at the onset of clinical signs. Animals were monitored on an hourly basis for 14 or 21 days. In the PEP study, all animals tolerated equine based antitoxin without any adverse clinical signs. A 100% survival was observed in groups treated with the BAT compared to 0% survival in those treated with the placebo (p<0.001, Fisher's exact test). BAT antitoxin prevented the development of signs of neurotoxicity of botulinum toxin. In a therapeutic study, treatment with the BAT at scaled 1x human dose after the onset of clinical signs significantly enhanced survival compared to the placebo (46.6% vs. 0%, p<0.0001, Fisher's exact test). Additionally, treatment with the BAT delayed the progression of signs (muscular weakness, respiratory distress, oral/nasal discharge) of toxin intoxication and reduced the severity of the disease.A single dose of BAT, when administered to symptomatic monkeys, resulted in a statistically significant survival benefit compared to the placebo. Additionally, BAT completely protected monkeys from the clinical signs of intoxication and subsequent death when administered as PEP treatment. These data in part supported the licensure of BAT under the Animal Rule in the United States by the Food and Drug Administration. |
| first_indexed | 2024-12-10T20:59:36Z |
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| id | doaj.art-2757d1a62d78483aae5b7739b2268d8b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T20:59:36Z |
| publishDate | 2017-01-01 |
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| spelling | doaj.art-2757d1a62d78483aae5b7739b2268d8b2022-12-22T01:33:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-011211e018689210.1371/journal.pone.0186892Therapeutic efficacy of equine botulism antitoxin in Rhesus macaques.Shantha KodihalliAndrew EmanuelTeresa TaklaYi HuaCharles HobbsRoss LeClaireDenise C O'DonnellThere are currently no licensed vaccines available for prevention of botulism in humans. The vaccination is not desirable due to expanding therapeutic indications of botulinum toxins. The only available specific treatment for botulism is antitoxin to remove circulating toxin, thus, preventing further neuronal damage. BAT® (Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G)-(Equine)) has been developed and its therapeutic efficacy evaluated against botulinum neurotoxin serotype A (BoNT/A) in Rhesus macaques.In a post-exposure prophylaxis (PEP) study, animals were exposed to 4x LD50/kg of BoNT/A and administered intravenously with either BAT (1x or 0.1x scaled human dose), or placebo at 4 hours post-exposure. The animals were monitored for 14 days. For the therapeutic intervention studies, animals were exposed to a 1.7x LD50/kg of BoNT/A and treated intravenously with either placebo or BAT at a 1x scaled human dose at the onset of clinical signs. Animals were monitored on an hourly basis for 14 or 21 days. In the PEP study, all animals tolerated equine based antitoxin without any adverse clinical signs. A 100% survival was observed in groups treated with the BAT compared to 0% survival in those treated with the placebo (p<0.001, Fisher's exact test). BAT antitoxin prevented the development of signs of neurotoxicity of botulinum toxin. In a therapeutic study, treatment with the BAT at scaled 1x human dose after the onset of clinical signs significantly enhanced survival compared to the placebo (46.6% vs. 0%, p<0.0001, Fisher's exact test). Additionally, treatment with the BAT delayed the progression of signs (muscular weakness, respiratory distress, oral/nasal discharge) of toxin intoxication and reduced the severity of the disease.A single dose of BAT, when administered to symptomatic monkeys, resulted in a statistically significant survival benefit compared to the placebo. Additionally, BAT completely protected monkeys from the clinical signs of intoxication and subsequent death when administered as PEP treatment. These data in part supported the licensure of BAT under the Animal Rule in the United States by the Food and Drug Administration.http://europepmc.org/articles/PMC5699824?pdf=render |
| spellingShingle | Shantha Kodihalli Andrew Emanuel Teresa Takla Yi Hua Charles Hobbs Ross LeClaire Denise C O'Donnell Therapeutic efficacy of equine botulism antitoxin in Rhesus macaques. PLoS ONE |
| title | Therapeutic efficacy of equine botulism antitoxin in Rhesus macaques. |
| title_full | Therapeutic efficacy of equine botulism antitoxin in Rhesus macaques. |
| title_fullStr | Therapeutic efficacy of equine botulism antitoxin in Rhesus macaques. |
| title_full_unstemmed | Therapeutic efficacy of equine botulism antitoxin in Rhesus macaques. |
| title_short | Therapeutic efficacy of equine botulism antitoxin in Rhesus macaques. |
| title_sort | therapeutic efficacy of equine botulism antitoxin in rhesus macaques |
| url | http://europepmc.org/articles/PMC5699824?pdf=render |
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