A potential therapeutic antibody, which could be used to neutralise a snake bite venom toxin, may actually enhance the toxin’s damaging effects, suggests a mouse model published in the journal Nature Communications. The findings may uncover a potential risk from an antibody which, according to laboratory experiments, could be used to neutralise a venom toxin from the pit viper Bothrops asper.
Every year, 2.7 million people are bitten by snakes globally and venomous snake bites kill and permanently disable hundreds of thousands of people. There is an urgent need globally for more safe and effective therapies to treat snake bites.
Limited effect
Current antivenom therapies using animal-derived blood serum are limited in their effectiveness, are expensive to produce, and can result in adverse immune reactions. This has led to researchers pursuing the development of recombinant antivenoms based on human antibodies. Previous studies have identified and characterised potential antibody-based therapeutics that have shown promising results in preclinical animal models of snakebite envenoming.
Bothrops asper viper venom contains myotoxin II, a substance that leads to muscle tissue destruction and can result in long-term disability or even death. Andreas Laustsen from the Technical University of Denmark and others identified potential antibody candidates to neutralise myotoxin II toxin in laboratory experiments. However, when they assessed their efficacy using a mouse model of snake envenoming, they found that the YTE-mutated IgG antibody actually enhanced the effect of the toxin, rather than neutralising it. These findings are the first demonstration of antibody-enhanced disease seen in this context and highlight the importance of thorough preclinical testing of antivenom candidates in more relevant contexts.
The authors highlight the need for careful consideration of antibody design and testing protocols to avoid unintended harmful effects. Further research is required to optimize these therapeutic antibodies and ensure their safety and efficacy in clinical settings. “While clinical ADET [antibody-dependent enhancement of toxicity] related to snake venom has not yet been reported in humans, this report of ADET of a toxin from the animal kingdom highlights the necessity of assessing even well-known antibody formats in representative preclinical models to evaluate their therapeutic utility against toxins or venoms,” they write. Whether this effect is unique to this particular antibody and toxin, or something that occurs more widely, and whether this is also seen in humans is yet to be determined.
