13 June 2024

Human antibodies used for the first time against black widow venom

Biotechnologists have succeeded for the first time in obtaining human antibodies that neutralise the venom of spiders of the black widow genus. Tests are still ongoing, but scientists are confident that their discovery will ensure an unlimited supply of a drug of constant quality and efficacy. In addition, it could be produced without involving animals.

A team of German biotechnologists from the Technical University of Braunschweig and medical scientists from the Carl Ludwig Institute of Physiology at the University of Leipzig, supported by YUMAB, PETA e.V. International Scientific Consortium and the Centre for Research and Higher Education in Mexico, reported the production of human antibodies that neutralise the venom of black widows (Latrodectus mactans). This is a genus of large predatory spiders that is distributed on all continents except Antarctica and has more than 30 species. The scientists' paper was published in the journal Frontiers in Immunology.

According to the American Association of Poison Control Centres, 1,134 patients bitten by black widows were recorded in the US in 2022. While these attacks are rarely fatal to humans, they can cause a syndrome called latrodectism. The reaction is triggered by the main protein component of the neurotoxic venom, alpha-latrotoxin (α-LTX).

In severe cases, latrodectism leads to increased sweating, nausea, vomiting, severe pain, muscle rigidity, i.e. constant tonic tension, heart problems and respiratory complications. It is a global health problem, especially in developing countries, the researchers emphasised.

Today, patients with latrodectism are treated with parenteral opioids combined with benzodiazepines, as well as polyclonal antiserums derived from the blood of immunised horses and containing antibodies of varying specificity. Such preparations are available, but their use carries risks due to their animal origin.

For example, allergic reactions (so-called serum sickness), including anaphylactic shock, can occur in humans. At least two patients who were previously injected with the horse antidote have died.

"The production of therapeutic drugs for horses is not governed by international guidelines or regulations to ensure animal welfare, with a few exceptions. In addition, extracting spider venom is costly and time-consuming. Wherever possible, animal products should be replaced with non-animal alternatives. Recombinant human antibodies can contribute to patient safety and avoid the use of animal products. In addition, they could be used to diagnose latrotoxin poisoning - to our knowledge, no such specialised method exists yet," explained the authors of the paper.

Applying various strategies phage display - a laboratory method for studying antibody interactions - the scientists selected 75 unique human antibodies that bind alpha-latrotoxin. Then 53 of the 75 antibodies were converted into IgG (immunoglobulins G) and successfully produced in vitro, in mammalian cell culture.

In summary, 45 of them were able to neutralise α-LTX of the European black widow, but it was the MRU44-4-A1 antibody that showed exceptionally high efficacy and affinity - the strength of interaction between individual sites of macromolecules that determines their affinity - in all assays.

"The antibodies we obtained may serve as a basis for future studies as potential therapeutic and diagnostic candidates. The fact is that for the first time they will provide an unlimited supply of a drug of consistent quality and efficacy, which, moreover, can be produced without the use of animals," the scientists summarised.

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