Each year, more than 100,000 lives are lost to snakebites, predominantly in Asia and Africa. Current antivenoms typically focus on specific snake species, leading to the need for multiple versions to tackle snakebites across different regions. This breakthrough represents a major step forward in creating a “universal antivenom” capable of neutralizing the venom from all snake species, offering a promising solution to this global health challenge.
The universal antivenom, 95Mat5
The Researchers at Scripps Research have uncovered an antibody, known as 95Mat5, which has demonstrated efficacy in neutralizing the venom of various poisonous snakes found across Africa, Asia, and Australia. Notably, this antibody effectively protected mice from the lethal effects of venoms from species such as black mambas and king cobras. Following years of focused research, the scientists have produced a promising antibody, 95Mat5 with the ability to counteract the deadly venoms of multiple snake species.
In this new study, various forms of laboratory-produced toxins were utilized to screen billions of human antibodies, resulting in the identification of one capable of inhibiting the toxins’ activity. This breakthrough signifies a significant advancement toward the development of a universal antivenom that could effectively neutralize the venom of all snake species.
The Three-Finger toxins
The researchers isolated and analyzed venom proteins from various elapids, a significant group of venomous snakes encompassing mambas, cobras, and kraits. Their investigation revealed that a specific protein type known as three-finger toxins (3FTx), present in all elapid snakes, contained similar sections across different species. Moreover, these 3FTx proteins, recognized for their high toxicity and role in inducing whole-body paralysis, emerged as promising targets for therapeutic interventions.
On the Way to Universal Antivenom
In their search for an antibody to block 3FTx, the researchers created a unique platform. They inserted genes for 16 different 3FTx into mammalian cells to produce the toxins in the lab. They then screened over fifty billion human antibodies to find ones that bound to the 3FTx protein from the many-banded krait, a species similar to other 3FTx proteins. This narrowed their search to about 3,800 antibodies. They tested these antibodies to see which ones also recognized four other 3FTx variants. Out of 30 antibodies found, one called 95Mat5 showed the strongest interactions with all toxin variants.
The researchers conducted tests on mice injected with toxins from the many-banded krait, Indian spitting cobra, black mamba, and king cobra to assess the impact of 95Mat5. In every instance, mice that received an injection of 95Mat5 alongside the toxins were not only shielded from death but also from paralysis.
Upon investigating the mechanism behind the effectiveness of 95Mat5 in blocking the 3FTx variants, the researchers found that the antibody mimicked the structure of the human protein typically targeted by 3FTx. Intriguingly, similar to this finding, the broad-acting HIV antibodies previously studied by Joseph Jardine, PhD also operate by mimicking a human protein.
Yet to Go More
Although 95Mat5 effectively counters the venom of all elapids, it does not inhibit the venom of vipers, the second group of venomous snakes. The team is currently working on creating broadly neutralizing antibodies against another elapid toxin and two viper toxins. They believe that combining 95Mat5 with these additional antibodies could offer extensive protection against numerous—or potentially all—snake venoms.
