An Efficient Method for Endotoxin Removal from Snake Antivenoms

Parenterally administered snake antivenom immunoglobulins are the only specific treatment for envenoming by snakebites. Endotoxin removal is a necessary part of good manufacturing practice for antivenom products to avoid life-threatening consequences associated with injecting endotoxin-contaminated...

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Bibliographic Details
Published in:Chromatographia 2020-06, Vol.83 (6), p.779-787
Main Authors: Sheraba, Norhan S., Diab, Mohamed R., Yassin, Aymen S., Amin, Magdy A., Alhamhoom, Yahya, Zedan, Hamdallah H.
Format: Article
Language:English
Subjects:
Affinity
Analytical Chemistry
Chemistry
Chemistry and Materials Science
Chromatography
Endotoxins
Immunoglobulins
Ion exchange
Laboratory Medicine
Low molecular weights
Optimization
Original
Pharmacy
Proteins
Proteomics
Recovery
Resins
Serum albumin
Ultrafiltration
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Summary:Parenterally administered snake antivenom immunoglobulins are the only specific treatment for envenoming by snakebites. Endotoxin removal is a necessary part of good manufacturing practice for antivenom products to avoid life-threatening consequences associated with injecting endotoxin-contaminated product. Optimization of pH is an essential factor in endotoxin purification. This study aimed to compare ultrafiltration, ion-exchange chromatography and affinity resin-based chromatography techniques at different pH values to select the depyrogenation method with the highest endotoxin removal efficiency and optimum protein/product recovery. Affinity resin-based chromatography achieved 91.2% protein recovery at acidic pH without detectable endotoxins, while ion-exchange chromatography achieved 74.42% protein recovery at pH 7.5. In contrast, ultrafiltration achieved the lowest protein recovery compared to other chromatography techniques. In addition, ultrafiltration was ineffective in removing serum albumin (~ 42–57 kDa) and low molecular weight (MW) Fc fragments (~ 24–31 kDa). In conclusion, affinity resin-based chromatography has proven to be the most effective endotoxin removal method, while ultrafiltration may not be appropriate for the removal of bacterial LPS from antivenom sera. Moreover, this study demonstrated the existence of an optimum pH for each chromatographic method for the purpose of producing sterile and endotoxin-free snake antivenoms.
ISSN:0009-5893
1612-1112
DOI:10.1007/s10337-020-03887-y