Snake antivenom

Snake antivenom
Clinical data
Other names	Snake antivenin, snake antivenene, snake venom antiserum, antivenom immunoglobulin
Identifiers
ChemSpider	none;

Last updated July 02, 2023

Snake antivenom is a medication made up of antibodies used to treat snake bites by venomous snakes.^[1] It is a type of antivenom.

It 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.^[2] The antibodies are then collected from the host animal, and further processed into snake antivenom for the treatment of envenomation.

It is on the World Health Organization's List of Essential Medicines.^[3]

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.^[4]

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.^[5] Cross neutralization affords antivenom manufacturers the ability to hyperimmunize with fewer venom types to produce geographically suitable antivenoms.

Availability

Snake antivenom is complicated for manufacturers to produce.^[6] When weighed against profitability (especially for sale in poorer regions), the result is that many snake antivenoms, world-wide, are very expensive. Availability, from region to region, also varies.^[7]

Antivenom shortage for New World coral snake

As of 2012^[update], the relative rarity of coral snake bites, combined with the high costs of producing and maintaining an antivenom supply, means that antivenom (also called "antivenin") production in the United States has ceased. According to Pfizer, the owner of the company that used to make the antivenom Coralmyn, it would take between $5–$10 million for researching a new synthetic antivenom.^{[ citation needed ]}^{[ clarification needed ]} The cost was too high in comparison to the small number of cases presented each year. The existing American coral snake antivenom stock technically expired in 2008, but the U.S. Food and Drug Administration has extended the expiration date every year through to at least 30 April 2017.^[8]^[9]

Foreign pharmaceutical manufacturers have produced other coral snake antivenoms, but the costs of licensing them in the United States have stalled availability.^[10] Instituto Bioclon is developing a coral snake antivenom.^[11] In 2013, Pfizer was reportedly working on a new batch of antivenom but had not announced when it would become available.^[9]As of 2016^[update], the Venom Immunochemistry, Pharmacology and Emergency Response (VIPER) institute of the University of Arizona College of Medicine was enrolling participants in a clinical trial of INA2013, a "novel antivenom," according to the Florida Poison Information Center.^[12]^[13]

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.

Types

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^[14]
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, Central and Eastern Sub-Saharan Africa polyvalent (EchiTAb-plus-ICP)	Carpet vipers (E. ocellatus), Puff adders (B. arietans), Black-necked spitting cobras (N. nigricollis)	Costa Rica
Antimicrurus	Coral snakes	Argentina
Coralmyn	Coral snakes	Mexico
Anti-micruricoscorales	Coral snakes	Colombia

Related Research Articles

<span class="mw-page-title-main">Antibody</span> Protein(s) forming a major part of an organisms immune system

An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the pathogen, called an antigen. Each tip of the "Y" of an antibody contains a paratope that is specific for one particular epitope on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can tag a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly.

Atracidae is a family of mygalomorph spiders, commonly known as Australian funnel-web spiders or atracids. It has been included as a subfamily of the Hexathelidae, but is now recognized as a separate family. All members of the family are native to Australia. Atracidae consists of three genera: Atrax, Hadronyche, and Illawarra, comprising 35 species. Some members of the family produce venom that is dangerous to humans, and bites by spiders of six of the species have caused severe injuries to victims. The bites of the Sydney funnel-web spider and northern tree-dwelling funnel-web spider are potentially deadly, but no fatalities have occurred since the introduction of modern first-aid techniques and antivenom.

Antivenom, also known as antivenin, venom antiserum, and antivenom immunoglobulin, is a specific treatment for envenomation. It is composed of antibodies and used to treat certain venomous bites and stings. Antivenoms are recommended only if there is significant toxicity or a high risk of toxicity. The specific antivenom needed depends on the species involved. It is given by injection.

A snakebite is an injury caused by the bite of a snake, especially a venomous snake. A common sign of a bite from a venomous snake is the presence of two puncture wounds from the animal's fangs. Sometimes venom injection from the bite may occur. This may result in redness, swelling, and severe pain at the area, which may take up to an hour to appear. Vomiting, blurred vision, tingling of the limbs, and sweating may result. Most bites are on the hands, arms, or legs. Fear following a bite is common with symptoms of a racing heart and feeling faint. The venom may cause bleeding, kidney failure, a severe allergic reaction, tissue death around the bite, or breathing problems. Bites may result in the loss of a limb or other chronic problems or even death.

Antiserum is a blood serum containing monoclonal or polyclonal antibodies that is used to spread passive immunity to many diseases via blood donation (plasmapheresis). For example, convalescent serum, passive antibody transfusion from a previous human survivor, used to be the only known effective treatment for ebola infection with a high success rate of 7 out of 8 patients surviving.

<span class="mw-page-title-main">Envenomation</span> Medical condition

Envenomation is the process by which venom is injected by the bite or sting of a venomous animal.

Crotalus scutulatus is a highly venomous pit viper species found in the deserts of the southwestern United States and central Mexico. It is perhaps best known for its potent neurotoxic-hemotoxic venom, which is considered the world's most potent rattlesnake venom.

Crotalidae Polyvalent Immune Fab (ovine), sold under the brandname CroFab, is a snake antivenin, indicated for North American Crotalid (Rattlesnake, Copperhead and Cottonmouth/Water moccasin) snake envenomation.

A spider bite, also known as arachnidism, is an injury resulting from the bite of a spider. The effects of most bites are not serious. Most bites result in mild symptoms around the area of the bite. Rarely they may produce a necrotic skin wound or severe pain.

Naja is a genus of venomous elapid snakes commonly known as cobras. Members of the genus Naja are the most widespread and the most widely recognized as "true" cobras. Various species occur in regions throughout Africa, Southwest Asia, South Asia, and Southeast Asia. Several other elapid species are also called "cobras", such as the king cobra and the rinkhals, but neither is a true cobra, in that they do not belong to the genus Naja, but instead each belong to monotypic genera Hemachatus and Ophiophagus.

Micrurus tener, commonly known as the Texas coral snake, is a species of venomous snake in the family Elapidae. The species is native to the southern United States and adjacent northeastern and central Mexico. Five subspecies are recognized as being valid, including the nominotypical subspecies, Micrurus tener tener, which is found in both the US and Mexico, and is also commonly known as the Texas coral snake. The species Micrurus tener was once considered to be a subspecies of the eastern coral snake.

Delta atracotoxin is a low-molecular-weight neurotoxic polypeptide found in the venom of the Sydney funnel-web spider.

Latrodectism is the illness caused by the bite of Latrodectus spiders. Pain, muscle rigidity, vomiting, and sweating are the symptoms of latrodectism.

Venomous fish are species of fish which produce strong mixtures of toxins harmful to humans which they deliberately deliver by means of a bite, sting, or stab, resulting in an envenomation. As a contrast, poisonous fish also produce a strong toxin, but they do not bite, sting, or stab to deliver the toxin, instead being poisonous to eat because the human digestive system does not destroy the toxin they contain in their bodies. Venomous fish do not necessarily cause poisoning if they are eaten, as the digestive system often destroys the venom.

The fragment antigen-binding region is a region on an antibody that binds to antigens. It is composed of one constant and one variable domain of each of the heavy and the light chain. The variable domain contains the paratope, comprising a set of complementarity-determining regions, at the amino terminal end of the monomer. Each arm of the Y thus binds an epitope on the antigen.

Micrurus fulvius, commonly known as the eastern coral snake, common coral snake, American cobra, and more, is a species of highly venomous coral snake in the family Elapidae. The species is endemic to the southeastern United States. It should not be confused with the scarlet snake or scarlet kingsnake, which are harmless mimics. No subspecies are currently recognized.

The Instituto Bioclon S.A. de C.V. was formed in 1990 to research and develop F(ab’)2 antivenoms. On May 6, 2015 they received approval from the FDA to commercialize ANAVIP becoming their second drug approved by the FDA after ANASCORP. Both are commercialized in the US by Rare Disease Therapeutics, Inc. The company is performing clinical trials to get approval for a third drug, ANALATRO, designed to treat black widow spider envenomation.

Recombinant antibodies are antibody fragments produced by using recombinant antibody coding genes. They mostly consist of a heavy and light chain of the variable region of immunoglobulin. Recombinant antibodies have many advantages in both medical and research applications, which make them a popular subject of exploration and new production against specific targets. The most commonly used form is the single chain variable fragment (scFv), which has shown the most promising traits exploitable in human medicine and research. In contrast to monoclonal antibodies produced by hybridoma technology, which may lose the capacity to produce the desired antibody over time or the antibody may undergo unwanted changes, which affect its functionality, recombinant antibodies produced in phage display maintain high standard of specificity and low immunogenicity.

ANAVIP is the trade name of a snake antivenin indicated for the management of adult and pediatric patients with North American rattlesnake envenomation. As defined by the FDA, the proper name is crotalidae immune F(ab')2 (equine). It is manufactured by Instituto Bioclon for Rare Disease Therapeutics in the United States.

References

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