Human Antibodies Offer Hope for Improved Black Widow Antivenom

Black widow bites can lead to severe illness, typically treated with antibodies derived from horses. However, this method carries safety risks. To improve safety, researchers have developed fully human antibodies capable of neutralizing the European black widow's alpha-latrotoxin.

These antibodies could provide a consistent and unlimited supply of effective treatment against latrodectism. Preclinical and clinical testing is required before these antibodies can be implemented in practice, according to the researchers.

Image Credit: Scott Delony/Shutterstock.comImage Credit: Scott Delony/Shutterstock.com

There are various types of widow spiders, including the Australian redback spider, multiple button spider species in South Africa, and black, red, and brown variations found in North and South America. The European black widow, Latrodectus tredecimguttatus, is native to the Mediterranean region of Europe. However, these widow spiders have been expanding their range due to climate change in recent years.

The disorder known as latrodectism, brought on by the neurotoxin alpha-latrotoxin in widow spider venom, targets the neurological system and produces symptoms like excruciating pain, headaches, nausea, and hypertension.

Although antibodies generated from horses can be used to treat black widow bites, German researchers are working to create entirely human antibodies to make the treatment safer for people.

For the first time, we present human antibodies which show neutralization of black widow spider venom in a cell-based assay, 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.”

Michael Hust, Biologist, Professor and Study Senior Author, Technical University of Braunschweig

The study was published in the journal Frontiers in Immunology.

Fishing for Proteins

Many patients bitten by black widows do not receive treatment due to concerns about antivenom made from horse-derived proteins. These foreign proteins can cause severe allergic reactions, serum sickness, and other adverse effects from proteins in antisera produced from non-human animal sources.

Hust said, “We set out to replace horse sera with recombinant human antibodies to get a better product for the patients and to avoid the use of horses for serum production.”

The researchers employed an in vitro technique known as antibody phage display to achieve this.

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.”

Michael Hust, Biologist, Professor and Study Senior Author, Technical University of Braunschweig

Antibodies engineered in this way can be reproduced with consistent quality because the DNA sequence of the human antibody is known. This method could also improve animal welfare, as it eliminates the need to immunize and bleed horses to produce black widow antitoxins.

Antibody Optimization

The group that worked with Hust produced antibody candidates that could be utilized in the creation of therapeutic antibodies. 45 out of 75 produced antibodies demonstrated alpha-latrotoxin neutralization in vitro. The MRU44-4-A1 antibody demonstrated exceptionally strong neutralization.

The fact that only two antibodies proved effective against the venom of other widow species astonished the researchers.

Hust pointed out, “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.”

Additionally, the researchers stated that more preclinical measures are required to assess the antibodies' effectiveness before beginning clinical trials.

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. 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 years.”

Michael Hust, Biologist, Professor and Study Senior Author, Technical University of Braunschweig

Source:
Journal reference:

Ruschig, M., et al. (2024) Human antibodies neutralizing the alpha-latrotoxin of the European black widow. Frontiers in Immunology. doi.org/10.3389/fimmu.2024.1407398

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