Antibodies you can eat: A therapeutic revolution from the Callewaert lab and collaborators

10 August 2019
Therapeutic antibodies are being used increasingly in the clinic for the treatment of various diseases. Yet, oral to gut targeting of antibodies remains a challenge due to their incapability to survive digestion and reach gastrointestinal tissues. Now, the labs of Nico Callewaert (VIB-UGent Center for Medical Biotechnology), Ann Depicker (VIB-UGent Center for Plant Systems Biology), Henri De Greve (VIB-VUB Center for Structural Biology) and Eric Cox (UGent Faculty of Veterinary Medicine) have developed a new antibody technology that combines the advantages of antibody-based therapies with the convenience of oral drug administration. Importantly, these antibodies are manufactured using yeast or soybean in a process as straightforward as food manufacturing. This work, led by Vikram Virdi, was published in Nature Biotechnology. This technology may have potential uses in various areas, from fighting veterinary and human gut infections, treating inflammatory and metabolic disorders, to the development of microbiome altering food supplements.

Did you grow up wanting tobe a scientist?
Vikram: “Well, as a curious child I wanted to be a scientist in a white coat, but it was much later, around 16 or 17 years of age, while watching a TV program on plantmade insulin, that I was captured by a fascination for molecular farming. This led me to pursue a PhD making VHH based antibodies in plants which, during my postdoc time, got refined and developed to the current innovation together with the guidance of my mentors
and advisors.”

Was there a specific ‘Aha-moment’ during thisresearch journey?
Vikram: “Discovering that monomeric-IgA-like bivalent VHHIgA works in the gut lumen just as well as the secretory VHH-IgA version was a pleasant surprise.  We couldn’t have predicted this, as it’s the secretory version that is found in our gut. This discovery was significant as it presented the possibility to produce the
single-gene-requiring VHHIgA antibodies in a variety of platforms. As we demonstrated, we could produce these VHHIgAs in soybean seeds and yeast cells of Pichia pastoris. A second serendipitous discovery was that
the yeast-secreted VHH-IgAs can be freeze-dried or spray-dried, just as milk powder is manufactured.
This preparation is stable for up to 2 years at room temperature and requires no encapsulation for oral delivery. These features are significant as they will ease manufacturing and further broaden the scope of applications.”

There were a lot of collaborators from different fields involved. How did this improve the scientific research?
Ann: “Producing antibodies in plants started quite naively. We had no idea how complicated it is to bring a pharmaceutical product, such as an antibody, to the market. It’s not so much the production, but the subsequent purification and quality control that gobbles up most of the budget. On top of that there are
the clinical trials to test the safety and efficacy of the antibody. So, it was really stimulating, inspiring
and eye-opening to have groups with complementary knowhow and facilities contributing to this project:
plant, industrial and biomedical biotech, food and feed processing, animal husbandry, and control of infectious diseases.
In fact, it was amazing to realize how incompetent we are as scientists from the moment we step out of our own expertise and comfort zone.”

What’s next? Are you going to follow up this groundbreaking research?
Vikram: “We are currently exploring the application of this technology to target human ailments such
as inflammatory bowel disease, Clostridium difficile, and others. We would like to explore the potential
for preventing enteric infections in resource-poor and/or post-disaster settings to prevent humanitarian
crises like the cholera epidemic in Haiti following the 2010 the earthquake. Being cold-chainfree, we envisage convenient deployment of the edible VHH-IgA together with the relief force. We would like to work towards
realizing this dream.”

What do you see on the horizon, based on this work?
Vikram: “We hope our work gives impetus to monomeric IgA-based passive mucosal immunization efforts, inspiring other non-invasive needle-free ways of antibody mediated protection.”

Ann: “An even greater social impact of this work is that these experiments in piglets can be used as model and proof of concept for preventing human gastrointestinal infections, such as traveler’s diarrhea, which is caused
by a gut-colonizing bacterium. Our results suggest that ingesting specific antibodies with one’s meals could prevent a variety of viral and bacterial gut infections in humans.”

Any reflections now that the work has culminated in a major publication?
Ann: “Looking back, I can say that I’m truly happy that I was able to contribute to societal progress through a combination of fundamental and applied research. Research that, I might add, was conceived to inch towards the realization of the United Nation’s Sustainable Development Goals. Not only gaining knowledge and understanding has given me a lot of satisfaction, but also collaborating on the development of products flowing from our fundamental research.”


​​

​​
Vikram Vird​i, Ann Depicker, Nico Callewaert