Snake antivenom

Snake antivenom, (snake antivenin, snake antivenene) is a biological product that typically consists of venom neutralizing antibodies derived from a host animal, such as a horse or sheep. The host animal is hyperimmunized to one or more snake venoms, a process which creates an immunological response that produces large numbers of neutralizing antibodies against various components (toxins) of the venom. The antibodies are then collected from the host animal, and further processed into snake antivenom for the treatment of envenomation. Internationally, snake antivenoms must conform to the standards of Pharmacopoeia and the World Health Organization (WHO).^[1]

Snake Venom

Snake venoms are used in the production of snake antivenom as hyperimmunizing antigens. Snake venoms are complex substances that, depending on the species, can contain a variety of toxins. Toxin components can include proteases, nucleases, phosphodiesterases, and other enzymes which disrupt physiological processes and cellular integrity. The venom toxins are largely classified as neurotoxins, cytotoxins, myotoxins, and cardiotoxins. Venomous snake bites may cause a variety of symptoms, including pain, swelling, tissue necrosis, hypotension, neuromuscular collapse, blood clotting dysfunction, respiratory paralysis, kidney failure, coma and death.

Manufacturing and Production

Antivenoms are typically produced using a donor animal, such as a horse or sheep. The donor animal is hyperimmunized with non-lethal doses of one or more venoms to produce a neutralizing antibody response. Then, at certain intervals, the blood from the donor animal is collected and neutralizing antibodies are purified from the blood to produce an antivenom.

Regulations

• Human Medicine: In the United States, antivenom production and distribution is regulated by the Food and Drug Administration.
• Veterinary Medicine: In the United States, antivenom production and distribution is regulated by the United States Department of Agriculture's Center for Veterinary Biologics.

Classification

Monovalent vs. polyvalent

Snake antivenom can be classified by which antigens (venoms) were used in the production process. If the hyperimmunizing venom is obtained from a single species, then it is considered a monovalent antivenom. If the antivenom contains neutralizing antibodies raised against two or more species of snakes, then the composition is considered polyvalent.

Antibody composition

Compositions of the antivenom can be classified as whole IgG, or fragments of IgG. Whole antibody products consist of the entire antibody molecule, often immunoglobulin G (IgG), whereas antibody fragments are derived by digesting the whole IgG into Fab (monomeric binding) or F(ab')2 (dimeric binding). The fragment antigen binding, or Fab, is the selective antigen binding region. An antibody, such as IgG, can be digested by papain to produce three fragments: two Fab fragments and one Fc fragment. An antibody can also be digested by pepsin to produce two fragments: a F(ab')₂ fragment and a pFc' fragment. The fragment antigen-binding (Fab fragment) is a region on an antibody that binds to antigens, such as venoms. The molecular size of Fab is approximately 50kDa, making it smaller than F(ab')₂ which is approximately 110kDa. These size differences greatly affect the tissue distribution and rates of elimination.

Cross neutralization properties

Antivenoms may also have some cross protection against a variety of venoms from snakes within the same family or genera. For instance, Antivipmyn (Instituto Bioclon) is made from the venoms of Crotalus durissus and Bothrops asper. Antivipmyn has been shown to cross neutralize the venoms from all North American pit vipers.^[2] Cross neutralization affords antivenom manufacturers the ability to hyperimmunize with fewer venom types to produce geographically suitable antivenoms.

Families of venomous snakes

Over 600 species are known to be venomous—about a quarter of all snake species. The following table lists some major species.

Family	Description
Atractaspididae (atractaspidids)	Burrowing asps, mole vipers, stiletto snakes.
Colubridae (colubrids)	Most are harmless, but others have toxic saliva and at least five species, including the boomslang (Dispholidus typus), have caused human fatalities.
Elapidae (elapids)	Sea snakes, Taipans, Brown snakes, Coral snakes, Kraits, King Cobra, Mambas, Cobras.
Viperidae (viperids)	True vipers and pit vipers, including rattlesnakes and copperheads and cottonmouths.

Snake antivenom manufacturers and Research institutions

Bioclon Institute (Instituto Bioclon) Calzada de Tlalpan no. 4687, Col. Toriello Guerra. C.P. 14050, Mexico D.F. Tel: [phone]

BioVeteria Life Sciences, LLC 1042 Willow Creek Rd: A101-482, Prescott, AZ 86301 USA Tel: [phone]

Haffkine Bio-Pharmaceutical Corporation Limited. Mumbai, India. Telephone:[phone]

BTG International Ltd 5 Fleet Place, London EC4M 7RD, UK Tel: + 44 (0)20 7575 0000

Butantan Institute Av. Vital Brasil, 1500 - Butantãn - 05503-900, São Paulo, SP, Brasil Tel.: [phone]

CSL Poplar Road 45, 3052 Victoria Parkville Tel:[phone],

Clodomiro Picado Institute (Instituto Clodomiro Picado - ICP) Facultad de Microbiología, Universidad de Costa Rica, San Jose, Costa Rica Tel: [phone] Fax: [phone] http://icp.ucr.ac.cr or http://www.echitabplusicp.org

Central Research Institute 173204 Kasauli (H.P.), India Tel:[phone]

Institut Pasteur de Tunis 13 Place Pasteur, B.P. 74, Tunis, Tunisia Tel:[phone]

MicroPharm Ltd. Station Road Industrial Estate, Newcastle Emlyn, Carmarthenshire, SA38 9BY, United Kingdom Tel: [phone]

National Antivenom and Vaccine Production Centre P.O. Box 22490, 11426 Riyadh, Saudi Arabia Tel:[phone]

Red Cross Thailand 1871 Terdprakiat Bld, Henry Dunant Rd, Patumwan, Bangkok 10330

Razi Vaccine and Serum Research Institute - Snake and Antivenum Research and Production Dep- list of Therapeutics Sera Alborz province-Emam Khomeini Street- Hesarak- Tel: [phone]

Sanofi Pasteur SA Avenue Pont Pasteur 2, cedex 07, 69367 Lyon, France

Types of snake antivenom

Antivenom	Species	Country
Polyvalent snake antivenom	South American Rattlesnake Crotalus durissus and fer-de-lance Bothrops asper	Mexico (Instituto Bioclon)
Polyvalent snake antivenom	South American Rattlesnake Crotalus durissus and fer-de-lance Bothrops asper	South America
Polyvalent snake antivenom	Saw-scaled Viper Echis carinatus, Russell's Viper Daboia russelli, Spectacled Cobra Naja naja, Common Krait Bungarus caeruleus	India
Death adder antivenom	Death adder	Australia
Taipan antivenom	Taipan	Australia
Black snake antivenom	Pseudechis spp.	Australia
Tiger snake antivenom	Australian copperheads, Tiger snakes, Pseudechis spp., Rough scaled snake	Australia
Brown snake antivenom	Brown snakes	Australia
Polyvalent snake antivenom	Many Australian snakes	Australia
Sea snake antivenom	Sea snakes	Australia
Vipera tab	Vipera spp.	UK
EchiTabG	Echis spp.	UK
Polyvalent crotalid antivenin (CroFab - Crotalidae Polyvalent Immune Fab (Ovine))	North American pit vipers (all rattlesnakes, copperheads, and cottonmouths)	North America
Soro antibotropicocrotalico	Pit vipers and rattlesnakes	Brazil
Antielapidico	Coral snakes	Brazil
SAIMR polyvalent antivenom	Mambas, Cobras, Rinkhalses, Puff adders (Unsuitable small adders: B. worthingtoni, B. atropos, B. caudalis, B. cornuta, B. heraldica, B. inornata, B. peringueyi, B. schneideri, B. xeropaga)	South Africa[3]
SAIMR echis antivenom	Saw-scaled vipers	South Africa
SAIMR Boomslang antivenom	Boomslang	South Africa
Panamerican serum	Coral snakes	Costa Rica
Anticoral	Coral snakes	Costa Rica
Anti-mipartitus antivenom	Coral snakes	Costa Rica
Anticoral monovalent	Coral snakes	Costa Rica
West Africa polyvalent (EchiTAb-plus-ICP)	Carpet vipers, Puff adders, Black-necked spitting cobras	Costa Rica
Antimicrurus	Coral snakes	Argentina
Coralmyn	Coral snakes	Mexico
Anti-micruricoscorales	Coral snakes	Colombia

References

1. Theakston RD, Warrell DA, Griffiths E (April 2003). "Report of a WHO workshop on the standardization and control of antivenoms". Toxicon 41 (5): 541–57. doi:10.1016/S0041-0101(02)00393-8. PMID 12676433.
2. EE Sanchez, et al. The efficacy of two antivenoms against the venom of North American snakes. Toxicon 41 (2003) 357–365.
3. Spawls, S; Branch B (1995). The Dangerous Snakes of Africa. Ralph Curtis Books. Dubai: Oriental Press. p. 192. ISBN 0-88359-029-8.

External links

• WHO Guidelines for the Production Control and Regulation of Snake Antivenom Immunoglobulins (2010).