Antibodies

New method facilitates the way to finding new antibodies

Tuesday 30 Jun 20

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Andreas Hougaard Laustsen
Associate Professor
DTU Bioengineering
+45 29 88 11 34

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Shirin Ahmadi
PhD student
DTU Bioengineering

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Mette Haagen Marcussen
Head of Communications
DTU Bioengineering
+45 23 71 23 10

Andreas Hougaard Laustsen

Associate Professor Andreas Hougaard Laustsen spearheads the research group Tropical Pharmacology Lab at DTU Bioengineering, where he works on developing new methods for the development of therapeutic antibodies and producing a new generation of antivenoms based on human antibodies with the help of BSc, MSc and PhD students, and postdocs.

Shirin Ahmadi

Shirin Ahmadi is a last year PhD student from the Tropical Pharmacology Lab. She has conducted her PhD thesis project on engineering broad-spectrum recombinant antibodies against cobra toxins. She hopes that results of her project may lead to the development of more affordable, high-tech solutions to the snakebite envenoming crisis in the tropical regions of the world.

Associate Professor Andreas Laustsen has developed a new method to quickly detect new broad-spectrum antibodies against snake venom. The method can also be used to find new antibodies against bacteria and viruses.

It was in the search for broad-spectrum human antibodies against snake venom that Associate Professor Andreas Laustsen found a new way to use the Nobel Prize-winning method, phage display. A way of using the method that makes it much faster and cheaper to detect broad-spectrum antibodies agains snake toxins, but also against bacteria and viruses.

Snake venoms are very complex. They contain many different proteins from different protein families, and no two snake species’ venoms are the same. Another challenges of treating snake bite victims is that the victim does not always know which snake he or she was bitten by. It therefore makes good sense to develop broad-spectrum human antibodies against snake venoms.

“It is no understatement to call this a research breakthrough in our field. With a very simple method, we show that it’s possible to find broad-spectrum antibodies against three cobra species, and we do it both quickly and cheaply,” says Andreas Hougaard Laustsen.

"The method’s prospects are promising and wide-ranging because it can be used not only to develop broad-spectrum antidotes, but also to discover broad-spectrum antibodies against bacteria and viruses, such as corona virus."
Shirin Ahmadi, PhD Student at DTU Bioengineering

The phage display method is a technology that mimics the human immune system in a test tube. Traditionally, when using this method, you pour the venom you want to find antibodies against into a test tube. A library of human antibodies is then added to the tube. The library consists of bacteriophages (viruses that attack bacteria) in which billions of different human antibodies have been cloned. Some of the antibodies will then bind to the toxic proteins (antigens) in the venom. This is how the toxin is neutralized.

Antibodies only bind to the antigens they recognize. So when you subsequently purify the results from the tube, only the antibodies that are effective against that specific venom remain. The experiment is repeated with the same venom two to three times, allowing the binding antibodies to compete in order to find the strongest ones. It was during this part of the process that Andreas Hougaard Laustsen had the idea to use the method to find broad-spectrum antibodies:

“Instead of repeating the experiment with the first venom (venom A), we took the antibodies we had just found to be effective against venom A and poured them over another venom (venom B) and thus found broad-spectrum antibodies that could neutralize both venom A and B," says Andreas Hougaard Laustsen. 

"It was amazing to see that "our" human antibodies had the ability to not only neutralize one venom, but several. They could even neutralize venoms we didn’t use in the experiments at all (venom C),” adds PhD student Shirin Ahmadi, who was the primary researcher in the execution of the experiments and is the lead author of the newly published article. According to her, this new way of using the method has promising prospects:

“The method’s prospects are promising and wide-ranging because it can be used not only to develop broad-spectrum antidotes, but also to discover broad-spectrum antibodies against bacteria and viruses, such as corona virus.”

Read the article Methodology for discovering broadly-neutralizing monoclonal antibodies against snake toxins in the scientific journal Scientific Reports.

Antibodies

Antibodies play a crucial role in the body’s defence against pathogens. They are a form of protein produced by the immune system which bind to foreign proteins from, e.g., bacteria or viruses and prevent them from growing and spreading or penetrating the neural pathways.

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