Human Antibodies Devised for Snakebite Treatment

Black mamba (Dick Culbert, Flickr)

3 Oct. 2018. An academic-industry team in Europe and Central America assembled a group of human antibodies that protects lab mice against venomous toxins from a dangerous African snake. Researchers from Technical University of Denmark or DTU, University of Costa Rica, and the company Iontas Ltd. describe their processes and findings in yesterday’s issue of the journal Nature Communications.

The team led by Andreas Hougaard Laustsen, a biotechnology professor at DTU in Kongens Lyngby and microbiologist José María Gutierrez at University of Costa Rica in San José, are seeking more reliable treatments for snakebite envenoming or poisoning. World Health Organization says snakebite is one of the world’s most neglected tropical diseases, with an estimated 2.7 million envenoming cases worldwide resulting in as many as 138,000 deaths, and amputations or permanent disabilities in 3 times that number. Many treatments today say the researchers, use antibodies from the blood in horses, which while effective in many cases, can also cause severe immune reactions in some recipients.

The researchers proposed a treatment derived instead from human antibodies, which would reduce some of the immune reaction risk from animal antibodies. Their first target was venom from the black mamba snake, described by National Geographic as “fast, nervous, lethally venomous, and when threatened, highly aggressive.” Venom from the 14-foot snake mainly contains dendrotoxins that work quickly on motor nerves to cause involuntary muscle contractions and paralysis.

The team from DTU and Costa Rica worked with colleagues from Iontas in Cambridge, U.K. that built a technology for discovery of human antibodies for therapeutics. The Iontas process uses phage-display methods that expose interactions among proteins, peptides, or nucleic acids. These screening techniques harness bacteriophages, viruses that infect bacteria to connect proteins or peptides to their genetic codes. The screening identified a number of potential  immunoglobulin G, or IgG antibodies, the most common antibody in blood, as candidates for neutralizing black mamba dendrotoxins.

In initial tests, the researchers found the individual candidate IgG antibodies working on their own could not counteract the dendrotoxins, which led to tests with combinations of antibodies. The team identified and produced a synthesized cocktail of 3 antibodies that in proof-of-concept experiments with lab mice show they can neutralize dendrotoxins, when injected simultaneously with black mamba venom.

In the study, researchers injected the antibody cocktail directly into the mice’s cerebrospinal fluid, which while neutralizing the dendrotoxins, is not likely to be a practical method in low-resource regions of the world where most snakebites occur. The team acknowledges they need a solution that can be injected intravenously. They also cite the need to develop rescue treatments, administered after a person is bitten.

Moreover, say the researchers, a practical solution for clinics is a single treatment that covers a number of snake poisons. “We have shown,” notes Laustsen in a DTU statement, “that it is possible to produce an experimental human-based antivenom against important toxins from one snake species, the black mamba. Before clinical testing of the antivenom on humans will make sense, it is relevant to develop more antibodies for the antivenom to give it a broader spectrum against several types of snake venom.”

Laustsen tells more about the research in the following video.

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