Therapeutic Antibodies to Snake Venoms

Theakston, R.D.G.; Smith, Daniel

doi:10.1007/978-1-4471-1937-1_6

Cited by 12 publications

(6 citation statements)

References 68 publications

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“…Unlike conventional antivenoms, which consist mainly of F(abЈ) 2 fragments obtained by pepsin digestion of concentrated IgG, this new antivenom consists of monomer Fab fragments obtained by papain digestion of sheep IgG. 11 The Fab fragments have the theoretical advantages over F(abЈ) 2 fragments of being more rapidly distributed in the tissues, having a larger apparent volume of distribution, and carrying less risk of early antivenom reactions, which are thought to be the result of complement activation by residual Fc and cross-linked aggregates. These fragments possess only one binding site and so cannot form immune complexes.…”

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confidence: 99%

A new monospecific ovine Fab fragment antivenom for treatment of envenoming by the Sri Lankan Russell's viper (Daboia Russelii Russelii): a preliminary dose-finding and pharmacokinetic study.

Ariaratnam¹,

Meyer²,

Perera³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. Russell's viper is the most important cause of life-threatening snake bite and acute renal failure in Sri Lanka. Only equine polyspecific antivenoms imported from India are available. They have not proved effective clinically or in clearing venom antigenemia and they frequently cause reactions. In an attempt to reduce mortality and morbidity, a new monospecific ovine Fab fragment antivenom (PolongaTab ; Therapeutic Antibodies, Inc., London, United Kingdom) was raised against Sri Lankan Russell's viper venom. In a preliminary dose-finding study in 35 patients, an initial dose of 3-4 g restored blood coagulability permanently and stopped systemic bleeding, even in severely envenomed patients. Venom antigenemia disappeared within 1 hr of antivenom treatment but recurred, probably as a result of continued absorption of venom from the site of the bite, after the rapid clearance of therapeutic antibody. Twelve patients (34%) experienced early reactions that were usually mild and always responded to epinephrine.

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confidence: 99%

A new monospecific ovine Fab fragment antivenom for treatment of envenoming by the Sri Lankan Russell's viper (Daboia Russelii Russelii): a preliminary dose-finding and pharmacokinetic study.

Ariaratnam¹,

Meyer²,

Perera³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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“…Recently, attempts have been made to assess a novel, ovine, Fab antivenom, puri® ed by papain digestion, raised against Nigerian E. ocellatus venom (Smith et al,1992;Laing et al, 1995;Theakston and Smith, 1995). Prelim inary studies have yielded promising results (Meyer et al, 1997).…”

Section: Recent Advancesmentioning

confidence: 99%

“…The antivenoms produced usually comprise a concentrated F(ab9 )2 fragment of the IgG molecule, separated from the Fc component by pepsin digestion. However, recent developm ents in immunotherapy include the use of smaller, possibly less reactive Fab fragments prepared from the whole IgG molecule by papain digestion (Smith et al, 1992;Theakston and Smith, 1995).…”

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confidence: 99%

An objective approach to antivenom therapy and assessment of first aid measures in snake bite

Theakston¹

1997

Annals of Tropical Medicine And Parasitology

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Treatment of systemic envenoming in snake-bite victims has, in the past, depended almost entirely on the individual clinician's experience in assessing the severity of envenoming. The efficacy of treatment is obviously related to the neutralizing potency of the antivenom used, the route by which it is administered and the dose. The development of enzyme immunoassays has permitted a more scientific appraisal, allowing estimation of circulating specific venom and antivenom concentrations at any time after the bite in the patient's blood. It is therefore possible to measure accurately the efficacy of antivenom in the neutralization and clearance of venom antigen. In Brazil, it appears that clinicians treat patients with excessive amounts of highly efficient antivenoms and this results in an unacceptably high incidence of reactions. In Sri Lanka, the use of imported, Indian antivenom is relatively ineffective in neutralizing the venoms of Sri Lankan snakes, demonstrating the real problem of venom variability within individual species. In West Africa, the improved clearance of venom following treatment of Echis victims with a monospecific as opposed to a polyspecific antivenom has been demonstrated, and new, smaller fragment, Fab antivenoms have been developed and are now under clinical assessment. Such clinically-based immunological studies should result in more efficient and controlled use of expensive antivenoms for treatment of systemic envenoming and the accurate assessment of newly designed products. Such studies also emphasise the importance of individual countries producing their own antivenoms for treatment of systemic envenoming. Likewise, the use of such objective systems now enables the use of first-aid measures such as tourniquets to be properly assessed.

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“…Envenomations are widespread across the tropical regions of four continents (Africa, Asia, Australia, and the Americas) (10)(11)(12)(13), and antivenoms constitute the only known remedy for these injuries (12)(13)(14). Envenomations are widespread across the tropical regions of four continents (Africa, Asia, Australia, and the Americas) (10)(11)(12)(13), and antivenoms constitute the only known remedy for these injuries (12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

“…Envenomations are widespread across the tropical regions of four continents (Africa, Asia, Australia, and the Americas) (10)(11)(12)(13), and antivenoms constitute the only known remedy for these injuries (12)(13)(14). Because these antivenoms are extracted from animal hyperimmune sera, they are very potent in neutralizing venom effects as a result of their polyspecific characteristics that enable them to recognize and neutralize different epitopes or antigenic determinants on the venom molecule (12)(13)(14). Initially, antivenoms were administered as whole serum, which resulted in intolerance reactions in patients, the symptoms of which were referred to as "serum sickness".…”

Section: Introductionmentioning

confidence: 99%

Kinetics of Whole Serum and Prepurified IgG Digestion by Pepsin for F(ab')2 Manufacture

Boushaba¹,

Kumpalume²,

Slater³

2008

Biotechnol Progress

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An alternative route for the production of polyclonal F(ab')(2) fragments that might be adopted for the facile preparation of antivenoms is assessed in this work. The method involves the digestion of whole serum by free pepsin, which results in reduction of the number of processing steps commonly in use, because it avoids the initial purification of IgG's prior to their proteolytic cleavage by the enzyme. Digestion kinetics of whole serum and caprylic acid prepurified IgG using free pepsin were monitored with SDS-PAGE followed by densitometric analysis and antigen binding activity assay of the digested samples. It was observed that with equal units of pepsin activity, caprylic acid prepurified IgG was digested more rapidly than whole serum but that the overall retention of antigen binding activity was significantly greater in the latter case. The estimated first-order digestion rate parameters were 11.8 and 4.42 microM min(-)(1) for pure IgG and whole serum, respectively. The K(m) value obtained for whole serum digestion was 33 microM and that for pure IgG digestion was 43.5 microM. Calibration with undigested whole serum and pure IgG samples of known concentrations was performed using SDS-PAGE followed by image analysis. A linear relationship was observed between the protein concentration and the respective band intensity within the range of concentrations investigated (0.63-31.2 microM IgG concentration). This technique proved to be relatively rapid, reproducible, and more precise than size-exclusion chromatography as a result of its F(ab')(2)/IgG resolving power. Staining and destaining protocols were reproduced in terms of staining and destaining times, volumes added, and compositions. Furthermore, all digestion experiments were performed in duplicate sets to monitor the extent of variation of the digestion kinetic parameters measured by this method. The results obtained from this technique confirm and quantify previous observations that pepsin digestion of whole serum is slower and easier to control than digestion of pure IgG and results in higher recovery of antigenic binding activity.

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Therapeutic Antibodies to Snake Venoms

Cited by 12 publications

References 68 publications

A new monospecific ovine Fab fragment antivenom for treatment of envenoming by the Sri Lankan Russell's viper (Daboia Russelii Russelii): a preliminary dose-finding and pharmacokinetic study.

A new monospecific ovine Fab fragment antivenom for treatment of envenoming by the Sri Lankan Russell's viper (Daboia Russelii Russelii): a preliminary dose-finding and pharmacokinetic study.

An objective approach to antivenom therapy and assessment of first aid measures in snake bite

Kinetics of Whole Serum and Prepurified IgG Digestion by Pepsin for F(ab')2 Manufacture

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