The impact of a low dose, low volume, multi-site immunization on the production of therapeutic antivenoms in Thailand.
Abstract: Therapeutic antivenom against snakes was first produced by Albert Calmette in 1894. Since then antivenoms have saved the life of countless snakebite victims. However, there are still many problems associated with antivenom production, for example variable percentage of responder horses, low neutralizing potency of antivenom, the large amount of snake venom needed for immunization and the difficulties encountered in producing potent polyvalent antivenoms. These problems have led to shortage and high cost of antivenom and, in some cases, failure of treatment. In 1997, a new immunization protocol for antivenom production was reported. It involves the injection of venom at low dose (approx. 2mg/horse) emulsified in Complete Freund's adjuvant in low volume (0.1-0.2 ml/site) in a total of 10 sites around the neck area of the horse. This immunization protocol has minimized the local reaction at the injection site thus allowing the use of the potent oil adjuvant. This, together with the increase in total surface area of the droplets, allow a more effective immune response to take place, e.g. enhancing the migration and activation of more antigen presenting cells and lymphocytes. The low dose, low volume multi-site immunization has resulted in dramatic improvements on the antivenom production in terms of amount of venom used for immunization, the time required to reach hyperimmune stage, the percent of responder horses and the potency of the antivenom. Furthermore, this protocol has made it possible to produce potent truly polyvalent antivenoms against several elapid and viperid snakes. This immunization protocol has alleviated various problems associated with antivenom production and has implications for immunization in general.
Publication Date: 2002-12-07 PubMed ID: 12467662DOI: 10.1016/s0041-0101(02)00209-xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research investigates the effectiveness of a low dose, low volume, multi-site immunization technique in the production of antivenoms in Thailand. The innovative approach significantly improved the potency and efficiency of antivenom production, creating potential advances for immunization processes.
Introduction and Background
- The study provides a historical backdrop, referencing the work of Albert Calmette in 1894, who first created therapeutic antivenom against snakes.
- Despite the significant role antivenoms play in saving lives from snakebite emergencies, the paper recognizes issues that plague antivenom production – including variability in horse response rates, low antivenom potency, excessive snake venom needed for immunization, and challenges in producing potent polyvalent antivenoms.
- The aforementioned problems have, in turn, led to the scarcity and high cost of antivenom, and sometimes, treatment failure.
New Immunization Protocol and its Mechanism
- In 1997, an innovative immunization protocol was reported. It involves injecting a low dose (around 2mg/horse) of venom emulsified in a Complete Freund’s adjuvant in low volume (0.1-0.2 ml/site) into ten different sites around the horse’s neck.
- The protocol minimizes local reactions at the injection site, permitting the use of potent oil adjuvant, and the increase of the total surface area of the droplets facilitates a more efficient immune response, thereby enhancing the activation and migration of more antigen-presenting cells and lymphocytes.
Benefits and Advances of the New Immunization Protocol
- The low dose, multi-site immunization process triggers substantial improvements in antivenom production with respect to the volume of venom necessary for immunization, time needed to reach hyperimmune stage, responder horse percentages, and the potency of the antivenom.
- This new method enables the production of potent, truly polyvalent antivenoms against various elapid and viperid snakes.
- Significantly, this protocol method addresses, if not entirely eliminates, many of the challenges surrounding antivenom production and offers potential insights for immunization protocols generally.
Cite This Article
APA
Sriprapat S, Aeksowan S, Sapsutthipas S, Chotwiwatthanakun C, Suttijitpaisal P, Pratanaphon R, Khow O, Sitprija V, Ratanabanangkoon K.
(2002).
The impact of a low dose, low volume, multi-site immunization on the production of therapeutic antivenoms in Thailand.
Toxicon, 41(1), 57-64.
https://doi.org/10.1016/s0041-0101(02)00209-x Publication
Researcher Affiliations
- Queen Saovabha Memorial Institute, 10330, Bangkok, Thailand.
MeSH Terms
- Animals
- Antivenins / administration & dosage
- Antivenins / biosynthesis
- Elapid Venoms
- Elapidae
- Horses
- Immunization
- Thailand
- Viper Venoms
- Viperidae
Citations
This article has been cited 7 times.- Hanley BP, Gross G. Venom immunization: IgG/IgE titers, safety, risk, and methods of the VIPRBITEM cohort. J Biol Methods 2024;11(4):e99010026.
- Ratanabanangkoon K. A Quest for a Universal Plasma-Derived Antivenom Against All Elapid Neurotoxic Snake Venoms. Front Immunol 2021;12:668328.
- Tan KY, Tan CH, Fung SY, Tan NH. Neutralization of the Principal Toxins from the Venoms of Thai Naja kaouthia and Malaysian Hydrophis schistosus: Insights into Toxin-Specific Neutralization by Two Different Antivenoms. Toxins (Basel) 2016 Mar 26;8(4):86.
- Wong KY, Tan CH, Tan NH. Venom and Purified Toxins of the Spectacled Cobra (Naja naja) from Pakistan: Insights into Toxicity and Antivenom Neutralization. Am J Trop Med Hyg 2016 Jun 1;94(6):1392-9.
- Sapsutthipas S, Leong PK, Akesowan S, Pratanaphon R, Tan NH, Ratanabanangkoon K. Effective equine immunization protocol for production of potent poly-specific antisera against Calloselasma rhodostoma, Cryptelytrops albolabris and Daboia siamensis. PLoS Negl Trop Dis 2015 Mar;9(3):e0003609.
- Khamehchian S, Zolfagharian H, Dounighi NM, Tebianian M, Madani R. Study on camel IgG purification: a new approach to prepare Naja Naja Oxiana antivenom as passive immunization for therapy. Hum Vaccin Immunother 2014;10(6):1633-8.
- Gilliam LL, Carmichael RC, Holbrook TC, Taylor JM, Ownby CL, McFarlane D, Payton ME. Antibody responses to natural rattlesnake envenomation and a rattlesnake toxoid vaccine in horses. Clin Vaccine Immunol 2013 May;20(5):732-7.
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