Camel antibodies and yeast: A promising double act on the way to more sustainable agriculture
Camel antibodies and yeast: A promising double act on the way to more sustainable agriculture
Innovative water usage and decreasing harmful crop protection agents usually come to mind when discussing sustainable agriculture. The fight against livestock diseases, however, gets far less attention, even though it's just as crucial for the future of our food production. For example, up to half of all piglets in nurseries are affected by post-weaning diarrhea. Antibiotics and zinc oxide fell out of favor as a remedy because they harm our health and the environment. Camel antibodies came to the rescue, not for the first time – but now joined by the powers of yeast.
Antibodies 2.0, aka nanobodies®
One day in 1989, Professor Raymond Hamers had his biology students detect antibodies in blood. They didn't want to use human blood for fear of infectious diseases such as HIV. They also didn't like the idea of killing a laboratory mouse for its blood. At this point, Hamers remembers that he still has dromedary blood left over from another study. The students take the blood from the freezer and get to work.
This coincidence has led to the discovery that dromedary – and, by extension, all camelid - antibodies have a unique structure. The antibodies bind to a hostile foreign substance much more easily, letting them fight an infection much faster. The effect of the antibodies was not new in itself, but they were much more potent than the mouse antibodies commonly used at the time. In other words, the potential seemed enormous. The power of these 'Antibodies 2.0' – later renamed nanobodies – would unfold over the following decades. It has now reached the pig pens of livestock farms.
First, however, we need to go back to the early 1990s. For further research, Hamers and his colleague Serge Muyldermans traveled to Morocco to buy a camel themselves at a Moroccan market – as they couldn't apply for funding anywhere. The two protected their promising discovery and took out a patent in 1992 for the entire sequence of camelid antibodies. After all, governments and large companies increasingly showed interest in this promising discovery. The establishment of the VIB (Flemish Institute for Biotechnology) in 1996 was a true catalyst. VIB not only focused on the research itself, but also on technology transfer to support its scientists with valorizing their findings. In 2001 Ablynx was created - the first VIB spin-off to focus entirely on medical applications with nanobodies.
In 2018, Ablynx launched its first medicine on the market – Caplacizumab – against the rare coagulation disorder aTTP. The same year, the French pharmaceutical giant Sanofi acquired Ablynx for 3.9 billion euros.
From humans to animals and agriculture
Ablynx was created to develop medicines for humans using nanobodies. The VIB spin-offs Confo Therapeutics (since 2015) and ExeVir Bio (since 2020) do the same – the latter focuses on, among other things, the fight against COVID-19. The listed biotech company Argenx – founded by three former Ablynx employees – is focused on cancer and autoimmune diseases.
But the antibodies are also making their presence known in agriculture. After years of research into nanobody technology at the VIB-VUB Center for Structural Biology, Jan Steyaert's lab set up 'agrobody' technology. This formed the seedbed for spin-offs such as Agrosavfe (since 2019 Biotalys that use the antibody technology to work on plant pathogens, with the biofungicide Evoca™ as the first result.
The 'bio' in 'biofungicide' says it all: many farmers are looking for natural alternatives to their crop protection products because Europe is banishing more and more chemical pesticides. And Biotalys reaps the benefits of this agrobody technology, which has the potential to revolutionize the agricultural sector, all the more so because livestock health is also at risk.
While biotalys tackles the issue of chemical pesticides, sustainable agriculture can only be achieved when livestock health is improved.
In 2021, Biotalys went public and raised almost 53 million euros to ramp up product development and put Evoca™ on the market.
Camel blood meets yeast
Until the early 2000s, many animal feeds contained small doses of antibiotics to protect animals against various diseases. The problem? Bacteria can become resistant to antibiotics in animals, just like in humans. These resistant bacteria can then spread to people and pose a threat when we need antibiotics. It's no wonder the EU has also banned the use of antibiotics in livestock. Zinc oxide was the alternative for antibiotics for a while but can no longer be used since 2022 as it harms the environment when it gets into the soil via manure. So, what happens now?
Let's go back to 2008 for a moment. Ann Depicker (VIB-UGent Center for Plant Systems Biology) shares her knowledge about plant-based antibodies – building on the groundwork of Muyldermans and Hamers – with Henri De Greve (VIB-VUB Center for Structural Biology), who is looking for a sustainable remedy for post-weaning diarrhea. This disease is caused by an E.coli bacterium and affects 25 to 50 percent of all piglets in Europe. Depicker and De Greve discover that Pichia pastoris, a type of yeast, can offer a solution. They bring Nico Callewaert (VIB-UGent Center for Medical Biotechnology) on board because he has been studying the potential of yeasts for years.
Yeast cells are known as excellent genetic model organisms: they are easy to manipulate and reproduce at lightning speed. This makes large-scale production possible at a low cost - two essential factors in the agricultural industry that guarantee a promising future for innovative technology. A new VIB spin-off is therefore launched in 2020: Animab. The 'ab' in that name stands for antibodies.
In 2020, Animab was launched to prevent post-weaning diarrhea. The French investment fund Seventure Partners, PMV, V-Bio Ventures, VIB, and Agri Investment Fund (of the Boerenbond) were all part of the deal.
More diseases in sight
The first application of the Animab technology was to combat the widespread post-weaning diarrhea in piglets. The antibodies replace the antibodies that the piglets should ingest via the sow's milk during their first weeks of life. Piglets are taken away from their mothers early – the sows have to start a new cycle of mating and farrowing – so they suddenly stop getting antibodies before they have built up immunity. Add to that the stress of a new pig-pen environment, and you get an increased sensitivity to viruses and bacteria.
Depicker, De Greve, and Callewaert could count on Eric Cox, professor of immunology at the Faculty of Veterinary Medicine at Ghent University, to help steer the experiments in the right direction. Their collaboration resulted in antibodies that can be given to piglets in powder form by mixing them with their food or drinking water. That is revolutionary since antibodies generally must be injected because they do not survive digestion.
Animab is now also examining other diseases in livestock. Within a few years, the spin-off wants to have products on the market for many more animal diseases than just post-weaning diarrhea. From innovations in human medicine to more sustainable agriculture: who would have thought that a forgotten bag of dromedary blood would have such an impact?
In November 2022, Animab successfully closed a Series A capital round and raised 10 million euros to market its edible antibody technology for the control of pathogens in farm animals. The venture capital fund Qbic III led the investment round with the participation of the existing investors (Seventure Partners, VIB, PMV, AIF, and V-Bio Ventures).