Most of today’s snakebite antivenoms are far from perfect. Typically manufactured from animal blood plasma, the antidotes often remain expensive, inconsistent, and difficult to scale across multiple snake species. But a new approach detailed today in the journal Nature may finally offer a major step forward to save countless lives, particularly in the world’s most rural and impoverished areas. According to one international research team’s recent findings, an antivenom superingredient exists in llamas and alpacas.
An elapid emergency
Venomous snakes account for around 10 percent of the estimated 4,000 known species in the world. Of those, only about 360 of them fall within the Elapidae family. But despite their comparatively small numbers, elapids like mambas, cobras, and rinkhals are among the world’s deadliest snakes. Over 300,000 venomous snakebites are reported every year in sub-Saharan Africa, frequently resulting in over 7,000 deaths and as many as 14,000 limb amputations.
“[Elapids] are among the deadliest because their venoms contain potent neurotoxins that act rapidly to induce paralysis and respiratory failure,” Anne Ljungars, a biological engineer at the Technical University of Denmark (DTU) and study co-author, tells Popular Science. “The small, highly diffusible toxins spread quickly through the body, and the lack of timely treatment and access to effective antivenoms further contributes to the high mortality and disability rates associated with these bites.”
What’s more, elapids are capable of producing particularly large quantities of venom and are often very large. For example, an adult black mamba (Dendroaspis polylepis), one of the planet’s deadliest elapids, regularly grows upwards of 10 feet long.
Enlisting help from alpacas and llamas
But as dangerous as elapids are to humans, other mammals contain their own potential protections. Alpacas and llamas naturally produce a special antibody variant known as heavy-chain-only antibodies. Ljungars and colleagues wondered if using these to specially engineer proteins called nanobodies (VHHs) might provide a new antivenom treatment path. To do this, they first immunized the camelids with venoms collected from 18 African snake species. Next, they extracted samples to construct phase display libraries—a process to study protein interactions by examining which proteins “display” on the surfaces of bacteriophages. A bacteriophage is a virus that replicates inside bacteria cells. From there, researchers could comb through the libraries to identify any broadly neutralizing nanobodies.
“Nanobodies have some key characteristics that are beneficial for antivenom development including high affinity binding similar to normal antibodies [and] small size, which makes them good for rapid deep tissue penetration and reducing local tissue damage,” says Ljungars.Â
They’re also comparatively cheap and highly stable, allowing them to be stored in adverse conditions like high temperatures. Ljungar explains that nanobodies also exhibit a low immunogenicity, making it safer and capable of administration even before snakebite symptoms begin to show themselves.
“Today’s treatments are typically given after symptoms occur since they suffer from the risk of causing adverse reactions,” she adds.
Funding a promising breakthrough
In laboratory trials with rodents, the new nanobody antivenom prevented the deaths of mice exposed to venoms from 17 of the 18 snake species. It even reduced tissue damage typically caused by some of the most toxic venoms. The treatment also outperformed the existing commercial antivenom, Inoserp PAN-AFRICA, in preventing necrosis and death in mice across all snake species. However, the study’s accompanying announcement also reports that the nanobodies are currently “only partially protective” against green and black mambas.
Despite this, Ljungar and her colleagues hope to move forward with their promising alternative antivenom in clinical trials. Their findings suggest that broader protection against elapid snakebites using fewer ingredients is on the horizon, contradicting the popular theory that the best antivenoms require large (and costly) amounts of antibodies. However, the biggest current hurdle reportedly isn’t the complexity of snake neurotoxins. It’s convincing the right people to invest in the endeavor.
“It is very costly to do both these things,” explains study co-author and DTU antibody specialist Andreas Hougaard Laustsen-Kiel. “It is hard to attract money to make a drug where the business case might not be fantastic, as most snakebite victims live in rural impoverished parts of countries with limited access to healthcare.”
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