Venom from snakes and other animals can have fatal effects if not treated. Venom is a toxic substance and includes various components, including neurotoxins. Consequently, the neurotoxins within the venom disrupt the nervous system and cause deleterious effects including paralysis, respiratory failure, and interreference of electrical impulses that regulate nerve and muscle function. Unfortunately, treatment against venomous bites is limited to species and accessibility; therefore, it is critical to create an effective, generalizable antivenom.
To generate a robust antivenom, scientists traditionally collect antibodies from an immunized host animal, such as a horse or sheep. The antibodies are then used to neutralize the neurotoxin released from the venom. While the traditional way of generating antivenom has shown to be effective, patients taking the antivenom often experience adverse effects. Additionally, the treatments could be specific to a region and species of snake. As a result, scientists are trying to develop antibodies that can be applied to various venous bites from different species and regions of the world.
A recent article in Cell, by Dr. Peter Kwong and others, created an antivenom using antibodies isolated from an immunized human donor. This antivenom has broad species benefit with minimal adverse effects. Specifically, they found this antivenom to be protective against venomous snakes including black mamba, king cobra, and tiger snakes. Kwong is the Richard J. Stock Professor of Medical Sciences and Professor of Biochemistry and Molecular Physics in the Vagelos College of Physicians and Surgeons at Columbia University.
Kwong and others used mouse models and other laboratory techniques to determine the optimal antivenom ‘cocktail’. Firstly, the team discovered a donor who had previously been exposed to various snake neurotoxins through immunizations. Researchers found that by this donor exposing himself to the venom of 16 different snake species, he generated antibodies effective against multiple neurotoxins. This a milestone in medical history, because of the donor’s hyper-immunity that can generate multiple antibodies at once. Additionally, the antibodies created have broad neutralizing effects and could provide the key to a universal antivenom.
To build an effective antivenom for patients, researchers created a testing panel with some of the world’s deadliest snakes. They then isolated targeted antibodies from the immunized donor that was specific to each venomous snake they had on the testing panel. Each antibody was tested in a mouse model to build a generalized cocktail.
The team made a cocktail of three separate components including two antibodies from the donor and a small molecule. The first antibody in the cocktail, LNX-D09, protected mice from a lethal dose of venom from six different snake species. The team then added a small molecule, varespladib, a toxin inhibitor that protected against three other venomous species. Finally, the second antibody, SNX-B03, elicited protection against all the species included on the panel. As a result, scientists were able to provide full protection for 13 out of 19 species.
Kwong and his team have generated an unparalleled antivenom that can protect patients from over ten different species. Scientists are now starting to test the antivenom in veterinary clinics on dogs that have been bitten by snakes. In the future, scientists hope to include a fourth antibody to provide protection over a wider array of venomous snake species. Consequently, the creation of an effective, generalizable antivenom can be readily accessible at a lower production cost and improve care for high-risk patients.
