Formulation of a liquid ovine Fab-based antivenom for the treatment of envenomation by the Nigerian carpet viper (Echis ocellatus)

Al-Abdulla, Ibrahim; Garnvwa, J.; Rawat, Sophia; Smith, David S.; Landon, J.; Nasidi, Abdulsalami

doi:10.1016/s0041-0101(03)00170-3

Cited by 29 publications

(9 citation statements)

References 13 publications

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“…In liquid form, antivenom requires preservatives, as well as, and more problematically, refrigeration at between 4 °C and 6 °C to maintain its potency. Lyophilised or freeze-dried products are also available, but to minimise cost and maximise ease of use, some are distributed in liquid form [140]. Moreover, warmer temperatures can lead to the formation of protein aggregates in liquid antivenom, which increase the chances of adverse reactions [141].…”

Section: Antivenom (Anti-snake Venom/venin/asv) and Its Associatedmentioning

confidence: 99%

The Urgent Need to Develop Novel Strategies for the Diagnosis and Treatment of Snakebites

Williams

Layfield

Vallance

et al. 2019

Toxins

103

106

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Snakebite envenoming (SBE) is a priority neglected tropical disease, which kills in excess of 100,000 people per year. Additionally, many millions of survivors also suffer through disabilities and long-term health consequences. The only treatment for SBE, antivenom, has a number of major associated problems, not least, adverse reactions and limited availability. This emphasises the necessity for urgent improvements to the management of this disease. Administration of antivenom is too frequently based on symptomatology, which results in wasting crucial time. The majority of SBE-affected regions rely on broad-spectrum polyvalent antivenoms that have a low content of case-specific efficacious immunoglobulins. Research into small molecular therapeutics such as varespladib/methyl-varespladib (PLA2 inhibitors) and batimastat/marimastat (metalloprotease inhibitors) suggest that such adjunctive treatments could be hugely beneficial to victims. Progress into toxin-specific monoclonal antibodies as well as alternative binding scaffolds such as aptamers hold much promise for future treatment strategies. SBE is not implicit during snakebite, due to venom metering. Thus, the delay between bite and symptom presentation is critical and when symptoms appear it may often already be too late to effectively treat SBE. The development of reliable diagnostical tools could therefore initiate a paradigm shift in the treatment of SBE. While the complete eradication of SBE is an impossibility, mitigation is in the pipeline, with new treatments and diagnostics rapidly emerging. Here we critically review the urgent necessity for the development of diagnostic tools and improved therapeutics to mitigate the deaths and disabilities caused by SBE.

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Section: Antivenom (Anti-snake Venom/venin/asv) and Its Associatedmentioning

confidence: 99%

The Urgent Need to Develop Novel Strategies for the Diagnosis and Treatment of Snakebites

Williams

Layfield

Vallance

et al. 2019

Toxins

103

106

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“…A previous study described the use of sorbitol for the stabilization of equine IgG and F(ab 0 ) 2 preparations obtained by affinity chromatography (Rodrigues-Silva et al, 1997), as well as of an F(ab 0 ) 2 antivenom generated by pepsin digestion and ammonium sulfate precipitation (Rodrigues-Silva et al, 1999). In contrast, addition of sorbitol or mannitol to Fab ovine-derived antivenom did not increase its thermal stability (Al-Abdulla et al, 2003). This suggests that the effect of polyols may vary depending on the active substance of particular antivenoms, i.e.…”

Section: Introductionmentioning

confidence: 99%

Stability of equine IgG antivenoms obtained by caprylic acid precipitation: Towards a liquid formulation stable at tropical room temperature

Segura

Herrera

González

et al. 2009

Toxicon

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Liquid formulations of antivenom require a cold chain for their distribution and storage, especially in tropical countries characterized by high temperature and humidity (climatic zone IV). Since cold chain is often deficient in many regions, there is a need to develop novel formulations of liquid antivenoms of higher stability at room temperatures. The effect of addition of the polyols mannitol and sorbitol on the thermal stability of caprylic acid-fractionated equine whole IgG antivenoms was assessed in preparations having different concentrations of protein and phenol. Results evidenced that: (1) turbidity increases proportionally to phenol and protein concentration. (2) After one year of storage at 25 degrees C, caprylic acid-purified antivenoms, formulated with or without polyols, did not show evidences of instability. (3) Formulation of antivenoms with 2.0 M sorbitol prevents the appearance of turbidity after one year storage at 37 degrees C; however, there was a partial loss in neutralizing potency in these conditions. Results suggest that formulation based on sorbitol is an option to obtain liquid whole IgG antivenoms of higher stability at tropical room temperatures.

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“…Specific antibody titres were determined by ELISA and when a plateau of immune response was reached (approximately 14 weeks after the first immunisation), 10 ml of blood per kg body weight was collected every four weeks. The IgG fraction was extracted from the ovine sera by the addition of caprylic acid (octanoic acid) followed by dilution with saline and mixed vigourously to precipitate non-IgG proteins 65 . The EBOTAb product was formulated in 20 mM citrate buffer (pH 6.0 ± 0.2) containing 153 nM NaCl and 0.1% Tween 20, pH 6.0.…”

Section: Methodsmentioning

confidence: 99%

Post-exposure treatment of non-human primates lethally infected with Ebola virus with EBOTAb, a purified ovine IgG product

Dowall

Jacquot

Landon

et al. 2017

Sci Rep

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Despite sporadic outbreaks of Ebola virus (EBOV) over the last 4 decades and the recent public health emergency in West Africa, there are still no approved vaccines or therapeutics for the treatment of acute EBOV disease (EVD). In response to the 2014 outbreak, an ovine immunoglobulin therapy was developed, termed EBOTAb. After promising results in the guinea pig model of EBOV infection, EBOTAb was tested in the cynomolgus macaque non-human primate model of lethal EBOV infection. To ensure stringent therapeutic testing conditions to replicate likely clinical usage, EBOTAb was first delivered 1, 2 or 3 days post-challenge with a lethal dose of EBOV. Results showed a protective effect of EBOTAb given post-exposurally, with survival rates decreasing with increasing time after challenge. Viremia results demonstrated that EBOTAb resulted in a decreased circulation of EBOV in the bloodstream. Additionally, assay of liver enzymes and histology analysis of local tissues identified differences between EBOTAb-treated and untreated groups. The results presented demonstrate that EBOTAb conferred protection against EBOV when given post-exposure and should be explored and developed further as a potential intervention strategy for future outbreaks, which are likely to occur.

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Formulation of a liquid ovine Fab-based antivenom for the treatment of envenomation by the Nigerian carpet viper (Echis ocellatus)

Cited by 29 publications

References 13 publications

The Urgent Need to Develop Novel Strategies for the Diagnosis and Treatment of Snakebites

The Urgent Need to Develop Novel Strategies for the Diagnosis and Treatment of Snakebites

Stability of equine IgG antivenoms obtained by caprylic acid precipitation: Towards a liquid formulation stable at tropical room temperature

Post-exposure treatment of non-human primates lethally infected with Ebola virus with EBOTAb, a purified ovine IgG product

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