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A Snake in the Grass, a Ray in the Sand: All About Antivenoms

A Snake in the Grass, a Ray in the Sand: All About Antivenoms

By Sol Vu

We discover what antivenoms are, how they’re made, and much more!

 

What is an Antivenom?

If you’ve been hiking, you may be familiar with warning signs along trails about snakes. One careless misstep during your hike may earn you a nasty bite from one of these creatures. Upon being ushered to a hospital after a snake bite, you may be administered antivenom.  

An antivenom is a substance made of antibodies that are used to neutralize venoms and mitigate their effects (such as death) [1,2,7]. They are similar to vaccines in that the end goal is to use antibodies to fight off or destroy whatever is harming you. But vaccines, such as the flu vaccine, aim to encourage your immune system to create antibodies to fight off a disease, whereas antivenoms use foreign antibodies from other sources [1,2,4].

 

How Are Antivenoms Made? 

Antivenoms are made by first obtaining a sample of venom. This is done by “milking” snakes which means to get them to bite onto a container and release their venom. These snakes can either be ones which are taken care of in captivity or wild-caught and then released.

After collecting the venom, a small, nonlethal sample will be administered to a horse or sheep. Care is taken to avoid harming the animals unnecessarily and the dose of venom is small enough to avoid death.

 

Blood will be drawn from the animal (so long as it is in good health). The red blood cells will be separated from the plasma. Plasma is the liquid part of blood which contains things like proteins. The plasma is then further purified and filtered to obtain immunoglobulins a.k.a. antibodies.

During this process, care must be taken to ensure there is no contamination which can result in infection if the antivenom is given to a person.

 

Components of Plasma Diagram. Taken from
Cleveland Clinic.https://my.clevelandclinic.org/health/body/22865-plasma 

 

Disadvantages of Antivenom

There are some downsides to antivenoms to keep in mind. 

One is that variability in the venom used to produce antivenom may impact effectiveness. Even if the venom is from snakes of the same species, variance exists in the venom due to factors such as diet or age [2,5,11]. 

Another disadvantage are adverse reactions to antivenom. Reactions can include headaches, vomiting, and severe – even life-threatening — allergic responses [2,3]. This may be because of sensitivity to the animal proteins and also impurities in the antivenom despite purification processes [3,13]. In the long-term, one may experience serum sickness. This is characterized by a delayed reaction to the antivenom by 5-14 days. During this time, one’s immune system will work against the antivenom because it recognizes the antibodies as foreign to their own body [9]. Symptoms will be similar to that of when one is sick such as a fever. Luckily, symptoms will usually subside on their own [9].

 

Viability of Stingray Antivenom 

As of writing this, there are no stingray antivenoms. But there is some promising research we can look at. 

A 2020 publication from the Federal University of Amazonas experimented with testing an antivenom for the spotted stingray (Potamotrygon motoro) which is a freshwater ray found widely in South America [12]. Samples of the venom were collected from rays by scraping from the barb. This sample was given to lab mice after which blood was collected and processed to obtain the antivenom. The effectiveness of the antivenom was determined by observing inflammation/swelling after injecting another group of lab mice with venom in their paws. Their paws were also collected and processed for cellular studies investigating the damage inflicted by the venom.

Potamotrygon motoro photographed by Steven G. Jonhson

Results indicate that antivenom made by vaccination was effective as an antivenom. The results are not statistically significant because of a low sample size of mice but are promising [12].

The most recent research about antivenoms for our round stingray (Urobatis halleri) is from 1972 [10]. Dr. Findlay Russell at the LAC/USC Medical Center investigated if the venom of the round stingray could be neutralized with antivenoms from the bat ray (Myliobatis californica) and the river stingray (Potamotrygon falkneri a.k.a. Potamotrygon castexi formerly Urobatis castexi). The results showed that the antivenoms provided some protection against round stingray venom but not complete protection. Unfortunately, it seems there wasn’t follow-up on this study yet. 

There is not enough research on round stingray venom to make an antivenom. In addition, antivenoms are costly to produce. Because little lethal threat is posed by stingray venom alone, there is less push for further development of antivenoms. At CSULB, the STABB Lab is investigating the venom of round rays and a possible antivenom.
Past studies may act as a guide to develop antivenoms for more species of stingrays.

  1. “Antivenoms.” World Health Organization, www.who.int/teams/control-of-neglected-tropical-diseases/snakebite-envenoming/antivenoms

  2. Alangode, Aswathy et. al “Snake antivenom: Challenges and alternate approaches” Biochemical Pharmacology. vol 181. 1141135. Nov, 2020. https://doi.org/10.1016/j.bcp.2020.114135

  3. de Silva, Asita H et. al “Adverse reactions to snake antivenom, their prevention and treatment” British Journal of Clinical Pharmacology. vol 81, 446-52. Mar 2016. doi: 10.1111/bcp.12739

  4. “Explaining How Vaccines Work”. Center for Disease Control. 10 Aug, 2024. https://www.cdc.gov/vaccines/basics/explaining-how-vaccines-work.html

  5. Fry, G. Bryan et. al “Effectiveness of Snake Antivenom: Species and Regional Venom Variation and Its Clinical Impact” Journal of Toxicology: Toxin Review. vol 22, 23-34. 5 Dec, 2003. https://doi.org/10.1081/TXR-120019018

  6. León, Guillermo et. al “Current technology for the industrial manufacture of snake antivenoms” Toxicon. vol 151, 63-73.  1 Sep, 2018. https://doi.org/10.1016/j.toxicon.2018.06.084

  7. Ratanabanangkoon, Kavi. “Polyvalent Snake Antivenoms: Productions Strategy and their Therapeutic Benefits” Toxins. 15, 517. 2023. https://doi.org/10.3390/toxins15090517

  8. Rathmore, S Anurag et. al “Recent advancements in snake antivenom production” International Journal of Biological Macromolecules. vol 240. 15 Jun, 2023. https://doi.org/10.1016/j.ijbiomac.2023.124478

  9. Rixe, Nancy and Tavarez,M. Melissa. “Serum Sickness” StatPearls. 2025 Jan. https://www.ncbi.nlm.nih.gov/sites/books/NBK538312/

  10.  Russell, Findlay. “Some Chemical and Zootoxicological Properties of Stingray Venom” University of Southern California. 31 Mar, 1972.

  11.  Smith, Cara et. al “Snakes on a plain: biotic and abiotic factors determine venom compositional variation in wide-ranging generalist rattlesnake” BMC Biology. vol 21, 136. 6 Jun, 2023. https://doi.org/10.1186/s12915-023-01626-x

  12. Varjão Lameiras, Juliana Luiza et. al “Neutralization of the edema-forming and myotoxic activities of the venom of Potamotrygon motoro Müller and Henle, 1841 (Chondrichthyes – Potamotrygoninae) by antivenoms and circulating immunoglobulins” Toxicon. vol 186, 126-140. 2020. https://doi.org/10.1016/j.toxicon.2020.08.006

  13. Xu, Jing et. al “Evaluation of the impact of antibody fragments on aggregation of intact molecules via size exclusion chromatography coupled with native mass spectrometry” MAbs. 27 Mar, 2024. doi: 10.1080/19420862.2024.2334783

 

This post was guest written by our friend Sol Vu, in collaboration with Dr. Ben Perlman and the STABB Lab

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