In order for vaccines to work as effectively as possible, natural oils such as squalene are used as active enhancers. The main resource of this oil is currently the livers of deep-sea sharks – millions of sharks die for it every year. But this adjuvant raw material can also be produced with the help of yeast, as researchers have now discovered. In large quantities, the microorganisms could become a sustainable source of the oil that is kind to the sharks and the environment.
In order for vaccines to prepare the immune system as well as possible for pathogens, auxiliary substances – so-called adjuvants – are often added to them. These substances strengthen the effect of the vaccine serums by ensuring that the vaccine is better absorbed by the cells and by intensifying the body’s immune response. As a result, there are fewer failures in the vaccine effect and a lower dose of the vaccine is required. In addition, thanks to the adjuvants, the vaccine also protects against germs that are similar to the pathogen.
Put an end to shark death
Doctors often use the lipid squalene as a vaccine booster. For years this oil has been extracted from the liver of deep-sea sharks, which are already endangered. Around 3,000 sharks die for one ton of squalene – environmental authorities estimate that up to three million animals are killed for the oil every year. Especially in times of the corona pandemic, this becomes a threat: According to the latest estimates, more than half a million sharks would have to be killed for a global corona vaccine.
That is why a research team led by Harald Pichler from the Austrian Center of Industrial Biotechnology and the University of Graz has now looked for an alternative and more environmentally friendly source of the important oil. The problem: Although plants such as sugar cane, amaranth or olive trees also belong to natural squalene producers, they produce significantly lower amounts of the lipid and are considered important foods. In addition, the squalene content in the plants depends on the temperatures, climate and soil conditions. Plant-based oil is therefore 30 percent more expensive than animal squalene.
Microorganisms as bearers of hope
For their study, the researchers examined microorganisms as a possible alternative oil source: To do this, they cultivated the yeast strain Saccharomyces cerevisiae – commercial baker’s yeast – in bioreactors. It was already known that this yeast strain can naturally produce the lipid, but only in small quantities. That is why the scientists used genetic engineering methods to increase the yeast oil production – and with success: “Since this yeast strain naturally already produces this lipid, we were able to use metabolic engineering to modulate certain metabolic pathways so that the yeast cells suddenly accumulate many times more squalene” , explains Pichler her discovery. As a result, the researchers received several grams of pure squalene in their study.
Their test is the world’s first proof that microorganisms can also produce large quantities of squalene in the laboratory. “We have proven that the process works on a laboratory scale,” summarizes Pichler. The researchers are now working on further developing the strains so that they can also be used in industry. “With industrial participation, squalene could be produced on a large scale in the future and therefore completely replace vegetable and animal sources of squalene,” says Pichler. Since squalene has already proven itself as a vaccine carrier in vaccines against influenza viruses and the coronaviruses SARS-CoV and MERS-CoV, the microbial adjuvant could also be helpful in potential corona vaccines, the research team suspects.
And that would have great long-term advantages: thanks to their rapid growth and adaptability, microorganisms can be multiplied in particularly large numbers and optimized for the production of squalene. They also provide the oil with a consistent quality. In addition, the nutrients for the microorganisms come from cheap and sustainable carbon sources such as food waste, agricultural biomass and molasses or from glycerine as a by-product of biodiesel production. Accordingly, they replace animal and vegetable sources for the production of the important adjuvants and thus protect the environment.
Source: Austrian Center of Industrial Biotechnology (ACIB)