Neutralization of Bee Venom Lethality by Immune Serum Antibodies

Schumacher, Michael J.; Egen, Ned B.; Tanner, David C.

doi:10.4269/ajtmh.1996.55.197

Cited by 28 publications

(29 citation statements)

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“…45 Venom from European and Africanized bees appeared identical when resolved by a sensitive electrophoresis system using differences in both the charge and size of the components. Based on this finding and their similar toxic properties and cross-reactivity, 14,21,37,46 it is probable that the antivenom raised against the European bee venom will be equally effective at neutralizing the venom of the Africanized bee.…”

Section: Discussionmentioning

confidence: 99%

“…Phospholipase A 2 is one of the most immunogenic components of bee venom and may contribute to the generalized toxicity of envenomation by a synergistic interaction with melittin. 3,[18][19][20][21]34 The antivenoms raised by immunizing with 1 or 4 mg of venom fully neutralized this important enzymatic activity. Melittin is also important, with its insertion into cell membranes being thought to cause disruption of the surrounding phospholipid bilayer, which allows phospholipase A 2 to gain access to its phospholipid substrate.…”

Section: Discussionmentioning

confidence: 99%

“…35 However, melittin is said to be poorly immunogenic probably because of its small size (26 amino acids with a molecular weight of 2,800 Da) and strongly hydrophobic regions. 3,21,34 It forms the major venom component and, fortunately, up to 4.5 g/L of specific antibodies to this peptide could be generated in sheep provided the period of immunization was sufficiently prolonged. The effects of the venom on the phrenic nerve diaphragm preparation were of a predominantly myotoxic type, as shown by both ultrastructural and functional changes.…”

Section: Discussionmentioning

confidence: 99%

“…14,21,37 The dramatic manifestations and rapid lethal effects produced by high venom concentrations in mice are probably due to apamin, which acts on the central nervous system. 16,[38][39][40][41] The antivenom was capable of neutralizing the venom in vivo when assessed using the standard efficacy (ED 50 ) test, and it was calculated that ϳ20.5 mg of antivenom was required to neutralize each milligram of venom.…”

Section: Discussionmentioning

confidence: 99%

“…[18][19][20] No specific therapy is available currently and a safe, effective treatment is urgently required. 4,21 We describe here the preclinical development and assessment of a specific A. mellifera antivenom that will hopefully prove suitable for treatment of mass bee attacks. …”

mentioning

confidence: 99%

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A novel Fab-based antivenom for the treatment of mass bee attacks.

Jones

Corteling²,

Bhogal³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. The frequency of mass bee attacks has dramatically increased in the Americas following the introduction and spread of the aggressive Africanized 'killer' bee (Apis mellifera scutellata). As yet no specific therapy is available, which led us to develop an ovine Fab-based antivenom as a potential new treatment. Sera from sheep immunized against the venom contained high levels of specific antibodies, as demonstrated by ELISA and by small-scale affinity chromatography, against both whole (A. m. mellifera) venom and purified melittin. A nerve muscle preparation was used to show the myotoxic effects of the venom and neutralization by the antivenom. Antivenom neutralizing ability was also demonstrated using assays for venom phospholipase A 2 and in vivo activities. Venom from both European and Africanized bees appeared identical when analyzed by acid-urea gel electrophoresis. This antivenom may therefore provide the first specific therapy for the treatment of mass envenomation by either European or Africanized 'killer' bees.The accidental introduction of the native African bee Apis mellifera scutellata into Brazil in 1957 and its subsequent displacement and hybridization of the long-established European bees A. m. mellifera and A. m. ligustica has resulted in the highly aggressive Africanized 'killer' bee. 1,2 It is better adapted to warmer climates than its European counterparts and, as a result, has been highly successful and spread rapidly throughout Latin America. In 1992, the Africanized bee crossed the border into the United States and is now found in Texas, Arizona, New Mexico, and southern California. 3 It is predicted to eventually be distributed as far east as North Carolina. 2 These bees attack much more readily and in greater numbers than the European varieties, 1 and thousands of stings may be inflicted on a single individual. 4,5 About 50 simultaneous stings can cause systemic envenoming and about 500 are probably necessary to cause death by direct toxicity, 4,6-10 although one death in Arizona was due to only ϳ125 stings. 11 By 1985, it was estimated that these bees had caused between 700 and 1,000 deaths, 12 and in Mexico there have been more than 190 such deaths between 1988 and 1993, with future estimates of 60 deaths per year. 13 Clinical features can include rhabdomyolysis, intravascular hemolysis, respiratory distress, hepatic dysfunction, hypertension, myocardial damage, shock, and/or renal failure. 4,5,8,11 Each Africanized bee injects an average of 94 g of venom in less than a minute, compared with 147 g for the slightly larger European bee, and circulating venom levels in patients of up to 3.8 mg/L have been recorded. 4,14,15 The venom contains many biologically active components such as melittin, phospholipase A 2 , apamin, mast cell degranulating peptide, hyaluronidase, histamine, and dopamine. 16 Of these, melittin is predominant (ϳ50% by dry weight) and can disrupt cell membranes and produce pores even at low concentrations. 16,17 Phospholipase A 2 enhances this membrane disruptio...

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Section: Discussionmentioning

confidence: 99%