The poison of some snakes can be fatal, unless you get the right antidote. Now doctors have developed an antiserum with the widest effect so far. It neutralizes the toxins of 19 of the world’s fatal snakes, including the Black Mamba and the Königskobra. The antiserum could also help against other snakes. This was made possible by a man’s unusual blood donation who had immunized himself hundreds of times against snake toxins. His antibodies suddenly make several toxins ineffective, as maused attempts. The antibody cocktail developed from it could be a model for other broadband countertifts and paves the way to a universal antiserum.
Millions of people are bitten by snakes every year, especially in rural areas of developing countries. This is fatal for around 100,000 bite victims. Because over 600 snake species inject poison mixtures from up to 70 different toxins that paralyze the nerves and lead to breathing arrest – not only in humans, but also when the snakes are prey. In order to neuralize these neurotoxins, antibodies are needed that specifically bind to the proteins exactly this poison and neutralize it. To make such countertoxes, horses or sheep have so far been given the toxins of individual snake species. The animals then form antibodies that can be removed from the blood and injected people if necessary.
This process is effective, but serious undesirable reactions can occur to the non-human antibodies. In addition, this method only delivers the antidote for a specific snake vintage. Often, however, the bitten do not know which type of snake they have met, which makes the anti-nerum selection considerably more difficult. In addition, not all countertoxes are in stock at any time and everywhere. So doctors have long been looking for a path to create a wide -effective or even universal antidote that neutralizes several toxins at once.
Antibodies made of hyperimmune donor
A team led by Jacob Glanville from Centivax in South San Francisco has now developed such an antidote based on the antibodies of a human donor. The man had immunized himself 856 times by deliberately injecting different snake toxins. “The donor had carried out hundreds of bites and self -conviction with escalating doses of 16 species of very fatal snakes over a period of almost 18 years, which would normally kill a horse,” reports Glanville. The doctors have now tested which antibodies have developed the man’s immune system and whether they can be used as an antidote.
The team isolated the antibodies from the B-memory cells from the blood of the donor and tested the neurotoxins they act against. They checked the ingredients of the poison mixtures of 19 snakes from the Elapid family, which are among the most deadliest in the world. This group comprises about half of all poisonous snake species, including mambas, cobras, taipane and kit. The tested snake species live in North America, Africa, Asia, Australia and Oceania. Glanville and his colleagues, who were insulated from the donor, then mice one or more of the 19 snake toxins. They gradually combined several antibodies into a cocktail that can neutralize as many poisons as possible at once.
Antiserum cocktail works around 19 snake toxins
It turned out that the man had actually formed different antibodies, each of which is effective against several snake neurotoxins. The antibodies bind to evolutionarily preserved sections of the toxic proteins, such as crystal analyzes and structural comparisons. In combination of these antibodies, an antiserum cocktail was created, which was able to neutralize all 19 snake poisons tested in the mouse attempt. In 13 types of snake, the antiserum offered complete protection, in the remaining species, partial protection, as the team reports. The mixture contained in the antidote contained only two human antibodies and the small molecule of Varespladib: The first antibody (LNX-D09) made the poisons of six of the tested snakes ineffective-including Kobras and Mambas-, the synthetic active ingredient varespladib three more poisons-of Taipanen and the Tigerotter-and the second antibody (SNX B03)) other species, including Kraits and Kobras.
The results of the mouse attempts suggest that this three -part cocktail could also be effective against many other elapids that were not tested in this study. The researchers around Glanville now want to test their antidote cocktail on dogs that are often brought to veterinary clinics in Australia due to snake. Afterwards, the broadband opposite is to be tested in clinical studies to humans. They want to further increase the effect of the cocktail and optimize the dosage. Since the antibodies are of human origin, Glanville and his colleagues hope for better tolerance than with previous opposite poisoning.
In addition, the researchers want to develop an antidote with the same methodology as with the elapids in the future that aims at the other large family of poison, the vipers. “The end product would possibly be a single Pan counterhot cocktail or we would make two-one for the Elapids and one for the vipers-since there are only one or the other snake group in some areas of the world,” explains senior author Peter Kwong from Columbia University. The technology could therefore be a model for other broadband opposites and paves the way to a universal antiserum.
Source: Jacob Glanville (Centivax) et al.; Cell, DOI: 10.1016/J.Cell.2025.03.050