The improvement of the therapeutic anti-Lachesis muta serum production in horses.
Abstract: The main features associated with pit viper envenomations include the intense local lesions such as oedema, necrosis, acute renal failure and other effects. The severity of these reactions to snakebite depends on the degree of envenomation. Lachesis muta venom (LMV) has weak lethal activity, but due to the large amount often inoculated, the effects are extremely severe and demand anti-venom with a high neutralizing capacity. LMV had the lowest neutralizing antibody induction capacity in horses when compared with that of other venoms. For example, Bothrops anti-venom serum neutralizes 180 times the equivalent LD(50) to Bothrops venom; Crotalus anti-venom neutralizes 250 LD(50) of this venom, while Lachesis anti-venom neutralizes only five LD(50) of the Lachesis toxins. To examine the reasons for this low antibody induction, the H(GP) mouse line, genetically selected for high antibody production received, at different times during immunization with sheep erythrocytes (SE), whole LMV and isolated venom fractions I-VI eluted by gel-filtration chromatography on Superdex75. The specific antibody responsiveness showed a partial, but significant suppression of the anti-SE antibody responses during the kinetics of the primary and even the secondary immunizations, after 50-100 microg of fractions IV and V administration 72-48 h before the first antigen injections. Fraction IV was then applied in a Superose 12 column and three samples were obtained. The peak IVA containing a component of Mr 27 kDa was liable with the immunosuppressive effect as made evident by its effect on the H mice anti-SE responses. Horses receiving the LMV exempt of fractions IV and V produce highly significant anti-Lachesis sera with a 45 LD(50) neutralizing activity, providing, for the first time, an efficient specific therapeutic heterologous serum for human use.
Publication Date: 2005-03-01 PubMed ID: 15733568DOI: 10.1016/j.toxicon.2004.12.006Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The study aimed to improve the production of anti-venom for Lachesis muta snake bites in horses by understanding the factors that contribute to the low antibody induction in response to the venom.
Research Background
- Pit viper envenomations caused by the Lachesis muta (a type of pit viper snake) result in severe local lesions including edema, necrosis, and acute renal failure. The severity of these reactions largely depends on the degree of envenomation.
- While Lachesis muta venom (LMV) has relatively weak lethal activity on its own, the severity of its effects comes from the large amounts typically injected during a snakebite, therefore requiring highly effective anti-venom.
- Previous comparisons showed that anti-venoms for other snake species such as Bothrops and Crotalus neutralize much more of these venoms than Lachesis anti-venom does of LMV.
Methodology
- The study used the H(GP) mouse line, which has been genetically selected for high antibody production, to test different venom fractions of LMV.
- Mice received, at different times, a combination of whole LMV and isolated LMV fractions I-VI, which had been separated via gel-filtration chromatography on Superdex75, along with sheep erythrocytes (SE).
- Two specific venom fractions, IV and V, were found to suppress the anti-SE antibody responses during principal and secondary immunizations. To narrow down the elements responsible, fraction IV was further refined, yielding a sample dubbed IVA containing a component of 27 kDa contributing to the immunosuppressive effect.
Results and Conclusion
- When horses were given LMV rendered void of fractions IV and V, they produced significantly more potent anti-Lachesis sera, reaching a neutralizing capacity of 45 LD(50), or 45 times the lethal dose where 50% of subjects die.
- This research then provides a more efficient and specific therapeutic serum for the treatment of Lachesis muta envenomation, enhancing the effectiveness of anti-venom for treating these snake bites in humans.
Cite This Article
APA
Stephano MA, Guidolin R, Higashi HG, Tambourgi DV, Sant'Anna OA.
(2005).
The improvement of the therapeutic anti-Lachesis muta serum production in horses.
Toxicon, 45(4), 467-473.
https://doi.org/10.1016/j.toxicon.2004.12.006 Publication
Researcher Affiliations
- Seção de Processamento de Plasmas Hiperimunes, Instituto Butantan, Avenida Vital Brazil, 1500, 05503-900 São Paulo, Brazil.
MeSH Terms
- Animals
- Antibody Formation / drug effects
- Antivenins / immunology
- Antivenins / metabolism
- Antivenins / therapeutic use
- Blood Coagulation / drug effects
- Chromatography, Gel
- Crotalid Venoms / chemistry
- Crotalid Venoms / toxicity
- Electrophoresis, Polyacrylamide Gel
- Horses
- Immunization
- Lethal Dose 50
- Mice
- Mice, Mutant Strains
- Neutralization Tests
- Snake Bites / immunology
- Snake Bites / therapy
Citations
This article has been cited 5 times.- Wiezel GA, Bordon KC, Silva RR, Gomes MS, Cabral H, Rodrigues VM, Ueberheide B, Arantes EC. Subproteome of Lachesis muta rhombeata venom and preliminary studies on LmrSP-4, a novel snake venom serine proteinase. J Venom Anim Toxins Incl Trop Dis 2019;25:e147018.
- Cordeiro FA, Coutinho BM, Wiezel GA, Bordon KCF, Bregge-Silva C, Rosa-Garzon NG, Cabral H, Ueberheide B, Arantes EC. Purification and enzymatic characterization of a novel metalloprotease from Lachesis muta rhombeata snake venom. J Venom Anim Toxins Incl Trop Dis 2018;24:32.
- Stransky S, Costal-Oliveira F, Lopes-de-Souza L, Guerra-Duarte C, Chávez-Olórtegui C, Braga VMM. In vitro assessment of cytotoxic activities of Lachesis muta muta snake venom. PLoS Negl Trop Dis 2018 Apr;12(4):e0006427.
- Cremonez CM, Leite FP, Bordon Kde C, Cerni FA, Cardoso IA, Gregório ZM, de Souza RC, de Souza AM, Arantes EC. Experimental Lachesis muta rhombeata envenomation and effects of soursop (Annona muricata) as natural antivenom. J Venom Anim Toxins Incl Trop Dis 2016;22:12.
- de Assis EB, Estevão-Costa MI, do Carmo Valentim A, Silva-Neto A, Agostini Cotta G, Alvarenga Mudado M, Richardson M, Fortes-Dias CL. Purification and complete primary structure of the first PLA2 from Lachesis stenophrys (the Central American Bushmaster) snake venom. Protein J 2008 Aug;27(5):327-33.
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