Black widow spiders are among the world’s most venomous spiders, with a toxin that attacks the nervous system. While their bites can be treated with an antidote derived from other animals, a treatment that fully comes from human antibodies would ultimately be safer to use. A team in Germany is now closer to developing this kind of treatment. The potential therapeutic is described in a study published June 12 in the journal Frontiers in Immunology.
“For the first time, we present human antibodies which show neutralization of black widow spider venom in a cell-based assay,” study co-author and Technical University of Braunschweig biologist Michael Hust said in a statement. “This is the first step to replace the horse sera that are still used to treat the severe symptoms after a black widow spider bite.”
[Related: Black widows battle their even deadlier cousins in a brutal spider war.]
Earth is home to numerous types of widow spiders, which are also called button spiders in some parts of Africa. The black, red, and brown varieties are common in North and South America, while Australia has the redback spider. The European black widow is primarily found in the Mediterranean region, but its habitat is expanding due to climate change.
A widow spider’s bite can cause latrodectism, a disease where the neurotoxin alpha-latrotoxin in the spider’s venom attacks the nervous system. It causes symptoms including severe pain, high blood pressure, headache, and nausea.
Since the available antivenoms are made from proteins derived from hoses, many patients bitten by black widows aren’t treated. The horse-derived substances are foreign to the human body and can cause undesirable side effects. One of these includes serum sickness–a reaction to proteins in antisera that is made from non-human animal sources. The currently available antivenom is also an undefined mix of antibodies that can vary from batch to batch, but is still the most efficient treatment option.
To fix this, the team on this study set out to replace the formula with horse antibodies with recombinant human antibodies. They used an in vitro method called antibody phage display.
“This approach uses extremely diverse gene collections of more than 10 billion different antibodies. From this large diversity of antibodies, phage display can fish out antibodies which can bind the desired target, in this case the toxin,” said Hust.
Antibodies engineered this way can also be reproduced in the same quality over and over again since the same DNA sequence of the human antibody is already known to scientists. Making antidotes from human antibodies can also improve animal welfare since the hoses won’t need to be immunized and bleeded to create black window anti-toxins.
[Related: Spider conversations decoded with the help of machine learning and contact microphones.]
The team initially created 75 antibodies that could be potential candidates for developing therapeutic antibodies. Of these, 45 showed in-vitro neutralization of the black widow spider’s alpha-latrotoxin neurotoxin. According to the study, one antibody called MRU44-4-A1, showed particularly high neutralization. However, only two of the antibodies were effective against the venom from other widow varieties.
In order to evaluate their efficacy before clinical trials can begin and develop more potential treatments to other spider toxins, additional preclinical steps and studies are needed.
“In another project, we have shown that we can develop human antibodies to treat diphtheria which are effective in in vivo studies. We intend to take the same steps for the black widow antivenom antibodies,” said Hust. “This is especially important because with the invasion of the spiders into new habitats, the incidence of latrodectism and the need for therapeutic alternatives might increase over the next [few] years.”
