Milk allergy, caseins and the journey to a hypoallergenic real vegan cheese

By Maria Andrea Gonzales

We have all heard about lactose intolerance — everyone has that one friend who can’t eat ice cream without getting a stomachache. But for a lot of people, a stomachache is not the only thing that happens after consuming dairy products, such as milk or cheese.  Some people can have issues beyond an intolerance to lactose, they can have an actual allergy to the milk proteins.  More than 200,000 people in the US are diagnosed with milk allergy every year, and it is the most common allergy in young children. After eating dairy, people with milk allergy suffer from a range of reactions. These symptoms can be mild, such as rashes and swelling, or they can be as severe as shock and the inability to breathe.

“​​Don't get lactose intolerance confused with a milk allergy. They're not the same thing. Lactose intolerance is when you can't digest lactose, the sugar found in dairy products. You'll often get symptoms like stomach pain, gas, and diarrhea. With a milk allergy, the symptoms affect more than just your digestive tract. A milk allergy is when your immune system thinks dairy is a foreign invader and attacks it by releasing chemicals called histamines. Symptoms can range from wheezing problems to vomiting and diarrhea.” -  https://www.webmd.com/allergies/milk-allergy

Luckily, with the power of biotechnology, scientists could potentially create hypoallergenic dairy — milk and dairy products that do not induce these kinds of reactions. Keep reading to find out how is Real Vegan Cheese currently working on this goal.

What is the science behind milk allergy?

To understand how allergic reactions from milk can be diminished, we first need to understand how it happens. Instead of involving the digestive system like lactose intolerance, dairy allergy involves the immune system, reacting to proteins found in milk the same way as it would react to a harmful pathogen. These proteins are called caseins. Most mammals have 4 kinds of casein: k‐casein, β‐casein, αS1‐casein and αS2‐casein (humans do not have αS2). Each of these types of casein have slight changes in their genetic sequence depending on the species. Research is being done on genetic engineering for removing food allergens from plants, e.g. to avoid peanut or gluten allergies, but usually those strategies center on removing the allergen from the food altogether. Casein proteins are what give milk its characteristic properties and nutritional value, as well as being crucial for cheesemaking, which is why simply removing them from milk would not solve the problem. Instead, we need to find other solutions so that the immune system of those affected with milk allergy would not recognize the caseins as pathogens anymore.

What are we currently doing about it?

In Real Vegan Cheese, we’re working on diving into the genetic sequence of caseins and comparing them between species, including humans. Human milk is hypoallergenic by nature — we all feed from it as infants — which is why we consider it the ‘gold standard’ of hypoallergenic caseins. However, we cannot just use human caseins for cheesemaking or we would end up with human cheese. This seems to make people uncomfortable and may affect flavor and texture profile. And last time our team talked to the FDA about using the human version of casein proteins, they strongly recommended against it because of  regulatory hurdles (because ingesting human recombinant casein could potentially induce autoimmune disease if the immune system inappropriately targets it). That is why we are instead focusing on genetically engineering cow caseins to be hypoallergenic, using human or less allergenic mammal casein sequences as a guide. 

Researchers have identified which regions of various caseins bind to the immune system’s antibodies, especially focusing on the αS1‐casein. These regions are known as epitopes, and they are what trigger the immune system to react. Once we know about existing epitopes, we can replace certain amino acids in them for the amino acids found in human casein at that same position. After we’ve designed the modified caseins, the next step is to synthesize the genetic sequence, insert it into yeast, and wait for them to produce the proteins. After adding fats and sugars, and following the standard cheesemaking process, we aim to end up with a real vegan hypoallergenic cheese. So far we have not yet seen anyone else working on this angle, except for one fascinating pilot study trying to use casein peptides to induce desensitization in cow’s milk allergy.

What’s next for hypoallergenic cheese?

As much as we would love to have a 100% vegan and hypoallergenic cheese out in the market already, we are still working on the core mission to develop open source cheese casein production technology.  Right now RVC has been working to get back into the lab after COVID shut down lab work since spring 2020. We are using the downtime from lab work, to research more deeply into questions like hypoallergenic cheeses, cheese texture, and the overall makeup of current alternative protein dairy startups.  We meet every Monday at 7 pm Pacific Time. Every two weeks, we have a science meeting to discuss some papers and how they apply to our project. The other weeks are administration weeks where we manage the backend of the project. However,  there are many ways you can support this project to help us make our dream a reality. The best way to help is to volunteer for the project — it doesn’t matter if you’re a scientist, student, or just a science enthusiast, there is room for everybody to lend a helping hand. Another great way to help is by donating to the project, as making science is, not surprisingly, not cheap. You can donate through our website. Lastly, if you cannot do either of the options but would still like to help, you can share the project and follow us on social media to keep up with our work.

Maria Andrea Gonzales is a 3rd year Bioengineering undergraduate in UTEC (Lima, Peru). She is currently an intern in Real Vegan Cheese, helping out in the search for hypoallergenic caseins and media article writing. Maria Andrea is passionate about synthetic biology, working on various research projects in the food and agrotech sector.