As dangerous spiders change their habitats in response to climate change, researchers are looking for new ways to treat venomous bites of the unwitting prey – like humans.
Antivenoms are usually developed by harvesting antibodies generated by other mammals – such as horses – in response to injection with the toxin, but a European team is looking at ways to use human defences instead.
It could help avoid some of the side effects that come from using animal-derived remedies against harmful poisons, such as anaphylaxis and serum sickness – a delayed reaction to antivenoms, antivirals and some antibiotics that can result in fever, rash and joint pain.
The focus of the research was the European black widow spider (Latrodectus tredecimguttatus).
This species shares the same genus as Australia’s redback spider (Latrodectus hasseltii), New Zealand’s katipō (Latrodectus katipo) and several North and South American black widows. The bite of the European species is painful and leads to symptoms common to the genus such as nausea, vomiting and muscle pains and spasms.
Normally the treatment would be to inject a horse with the toxin and ‘bleed out’ the animal to extract neutralising antibodies generated in response. But in this study, scientists used a technique called ‘phage display’ to see which of more than 10 billion human antibodies can demonstrate in vitro binding to neutralise the target toxins.
“This approach uses extremely diverse gene collections,” says Michael Hust, a biologist from the Technical University of Braunschweig, Germany.
“From this large diversity of antibodies, phage display can fish out antibodies which can bind the desired target, in this case, the toxin.”
Once identified, the antibodies with the best neutralising potential can be replicated, providing a precise defence against a spider’s venom. Around 45 antibodies were identified as potential candidates to neutralise the spider’s alpha-latrotoxin, but one – MRU44-4-A1 – was the standout.
Finding a broad-spectrum antibody that is effective against the toxins present in these other species’ venoms may prove challenging. Only two antibodies were found to be effective against other black widows.
“To develop a potential treatment for all latrotoxins, and not only the toxin of the European black widow, we would need further improved cross-reactive antibodies,” Hust says.
European black widow spiders, as with many species, are being discovered in new locations, likely due to favourable conditions expanding northward due to increasing global temperatures.
The arrival of potentially dangerous species will, Hust says, increase the demand for viable neutralising drugs, so developing an effective human-derived antivenom could help meet demand, and offset animal welfare concerns through the continued use of horses.
“With the invasion of the spiders into new habitats, the incidence of latrodectism [the short-term disease caused by the spider bite] and the need for therapeutic alternatives might increase over the next years,” Hust says.
The research is published in the journal Frontiers in Immunology.