Llama antibody library for making new drugs

Researchers from Wageningen University & Research are building a large library of llama antibodies. These special antibodies are used by scientists to develop drugs and vaccines against new infectious diseases such as COVID-19.

Llamas are famous for spitting, but not everyone knows that these animals also have a very unusual immune system. Llama antibodies (which protect the animal from invading viruses or bacteria) are smaller than those of all other animal species and humans. The part of the antibody that binds to the pathogen so that it can be switched off consists of only a single component. This is very interesting for researchers: they can use these so-called nanobodies for the development of new vaccines or medicines.

“Previously, it took a lot of effort and time, often 3 to 6 months, to generate and identify the specific llama nanobodies that bind to a virus protein,” explains researcher Michiel Harmsen of Wageningen Bioveterinary Research. “We vaccinated llamas with a virus protein and had to wait for their immune system to make the corresponding antibodies. We would then isolate the antibodies from llama blood. But now it is possible to skip that whole process. We are building a large library from which antibodies against any new pathogen can be isolated immediately.”

Llama antibody library

The researchers are building the ready-to-use llama antibody library by taking blood from the animals only once. From that blood they extract the many genes that code for various nanobodies against all kinds of pathogens. As many as 50 million different nanobody genes can be extracted from one animal. By repeating this procedure with blood from 20 to 100 llamas, the researchers can build a library with billions of different nanobody genes.

Blood from 20 to 100 llamas is being used to create a large library with one billion nanobody genes.

And this is how it works...

But how do they know which specific antibody to retrieve from the library when a new disease breaks out? “For a therapy aimed at a specific disease, we want to find a single antibody that is very effective against that disease. We can use phage display to select this one antibody that is effective as a medicine from a very large library of billions of antibodies”, explains Harmsen. “The experiment works like this: we stick the virus protein to the wall of a test tube. Then we add the llama antibody library as phages. Bacteriophages are viruses that infect bacteria and are therefore useful in the laboratory because they grow quickly. All phages contain antibodies as well as proteins and genes. The phages containing the genes for the desired antibodies attach to the virus protein on the wall of the test tube. After rinsing the test tube, only the phages with the desired antibodies remain.”

The nanobodies can be administered in various ways, such as a nasal spray. In that case a respiratory virus first encounters a layer of antibodies instead of nose or lung cells.

Faster medicine development

Harmsen believes it is a great advantage that the researchers no longer have to expose the llamas to a viral protein via vaccination. “This invasive procedure is no longer necessary. With the library of ready-to-use antibodies, we can also contribute to faster development of medicines or tools for diagnostics that are necessary to combat new infectious diseases. We can skip the months it takes to vaccinate llamas.”