Antiserum Effective Against 19 Venomous Snake Species
- Jenner Nex
- 2 days ago
- 4 min read
Three-Part Antitoxin Neutralizes Toxins of the Deadliest Snakes
Potent antidote: For the first time, physicians have developed a broadly effective antiserum against 19 deadly snake species – including mambas, cobras, taipans, and kraits. The new antitoxin neutralizes the neurotoxins of all venomous snakes, as mouse experiments suggest. The antitoxin was created from antibodies from a man who had immunized himself against snake venom hundreds of times. The antibody cocktail could serve as a model for other broad-spectrum antivenoms and lead to a universal antiserum.
Every year, around 100,000 people worldwide die from snakebites, especially in rural areas. Many snakes produce venom mixtures of up to 70 different toxins. Many of these toxins paralyze the nerves, causing paralysis, suffocation, and cardiac arrest in both prey and humans.
Disadvantages of Current Antidotes
To render these snake venoms harmless, active ingredients or antibodies are needed that specifically bind to the proteins of the respective venom and neutralize it. Currently, such antivenoms are usually produced by administering small doses of the toxins of individual snake species to horses or sheep. The animals then produce antibodies that can be extracted from their blood and injected into humans if necessary.
However, severe adverse reactions to the non-human antibodies can also occur. Furthermore, this method only ever provides the antidote for a specific snake venom. Often, however, the bitten person does not know which of the over 600 venomous snake species they have encountered, which makes antiserum selection considerably more difficult. DNA testing of the snake is not always possible. Furthermore, not all antivenoms are available at all times and in all places.
Antibodies from an Unusual Blood Donation
Physicians have therefore long been searching for a way to produce a broadly effective or even universal antivenom that neutralizes several toxins at once. Previous attempts mostly relied on synthetic antibodies. A team led by Jacob Glanville of the company Centivax in South San Francisco has now developed such an antidote based on the natural antibodies of a human donor.
The man had self-immunized 856 times by intentionally injecting himself with small doses of various snake venoms. "The donor had performed hundreds of bites and self-immunizations with escalating doses of 16 species of highly lethal snakes over a period of almost 18 years, which would normally kill a horse," reports Glanville.
Venom of 19 Elapids Tested
The doctors have now tested which antibodies the man's immune system had developed as a result and whether these could be used as an antidote. The team isolated the antibodies from the memory B cells in the donor's blood and tested which neurotoxins they were effective against.
The focus was on the neurotoxins of 19 snakes from the elapid family, which, according to the World Health Organization (WHO), are among the deadliest in the world. This group comprises about half of all venomous snake species, including mambas, cobras, taipans, and kraits. The tested snake species live in North America, Africa, Asia, Australia, and Oceania.
Glanville and his colleagues successively administered the antibodies isolated from the donor to mice that had received one or more of the 19 snake venoms. They gradually combined several antibodies into a cocktail capable of neutralizing as many venoms as possible at once.
Antiserum cocktail protects against all tested snakes
It turned out that the man had indeed produced several antibodies, each effective against several snake neurotoxins simultaneously. The antibodies bind to evolutionarily conserved segments of the venomous proteins, as crystal analyses and structural comparisons have shown.
By combining two of these antibodies with the small molecule varespladib, an antiserum cocktail was created that was able to neutralize all 19 snake venoms tested in mouse experiments. The antiserum provided complete protection against 13 snake species and partial protection against the remaining species, the team reports.
The first antibody contained in the antiserum cocktail (LNX-D09) neutralized the venoms of six of the tested snakes – primarily cobras and the black mamba. The synthetic active ingredient varespladib neutralized three other venoms – two taipans and the tiger snake – and the second antibody (SNX-B03) neutralized the venoms of the remaining species – including kraits, cobras, and otters.
Even broader protection?
The results from the mouse experiments suggest that this three-part cocktail could also be effective against many other elapids not tested in this study. Glanville's researchers now plan to further test their antivenom cocktail on dogs, which are frequently brought to veterinary clinics in Australia for snakebites.
The broad-spectrum antivenom will then be tested in human clinical trials. They aim to further increase the effectiveness of the cocktail and optimize the dosage. Since the antibodies are of human origin, Glanville and his colleagues hope for better tolerability than previous antivenoms.
Hope for a universal antivenom
Furthermore, the researchers plan to use the same methodology as for elapids to develop an antivenom targeting the other large family of venomous snakes, the vipers. "The end product could potentially be a single pan-antivet cocktail, or we could create two—one for the elapids and one for the vipers—since some areas of the world have only one or the other group of snakes," explains senior author Peter Kwong of Columbia University.
The technique could therefore serve as a model for other broad-spectrum antivenoms and pave the way for a universal antiserum.
(Cell, 2025; doi: 10.1016/j.cell.2025.03.050)
Source: Cell Press
