Vaccines save lives. Unless you’re a shark. Because then vaccines can cost you your life and even contribute to the extermination of your species. But there is hope.
If you have ever been vaccinated, chances are that you also had a shark component injected. Many vaccines contain squalene: a substance that is extracted from the liver of sharks. “It enhances the immune response the body generates to vaccines,” said researcher Christopher Fox Scientias.nl. “And thus contributes to better protection against disease (…) and ensures that less vaccine is needed to evoke an effective immune response.”
Vaccines
This makes squalene a crucial component of vaccines that are already in circulation, such as flu vaccines and vaccines against COVID-19. And candidate vaccines against, for example, malaria and tuberculosis – which are currently still being clinically tested – also gratefully appeal to it. There is no question that we need those vaccines; for example, corona vaccines save an estimated 20 million lives in the first year. And vaccines against TB – an infectious disease that still claimed 1.6 million lives in 2021 – and malaria – which affected 241 million people in 2021 and killed 619,000 people – can also achieve enormous health benefits. But the use of squalene in these important vaccines, as sharks worldwide are facing an increasingly difficult time, is nevertheless meeting with increasing resistance. There is also a fear that there will simply not be enough sharks left to meet our demand for squalene.
Looking for an alternative
Reason enough to look for an alternative to squalene. And that is exactly what scientists have now – successfully – done, as stated in the magazine npj Vaccines to read. In the magazine, the researchers announce that they have generated no fewer than 20 semi-synthetic alternatives to squalene.
In principle, squalene can be extracted from many shark species. But in most cases, manufacturers still rely on deep-sea sharks for this, scientist Catherine MacDonald, affiliated with the Rosenstiel School of Marine and Atmospheric Science and not involved in Fox’s research, previously told Scientias.nl. “The deep-sea sharks generally provide the largest quantities. Because they live in an area with little food, they rely heavily on their oil-rich livers for energy, which are also very important for their buoyancy – unlike many bony fish, sharks do not have an air-filled swim bladder to keep them afloat.” The fact that these sharks have been unwillingly bombarded as suppliers of squalene is disturbing for several reasons. “Deep-sea sharks generally grow very slowly and mature quite late.” It means very concretely that a killed sexually mature deep-sea shark is not so quickly replaced by a new adult shark. Their birth rates are also low. That makes them particularly vulnerable to overfishing.”
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Just as good or better
The researchers not only generated 20 semi-synthetic alternatives to squalene, but of course also tested them. They examined how the activity of the alternative substances when added to vaccines related to the activity of squalene. And those findings are also hopeful; some semi-synthetic alternatives have been found to work just as well or better than traditional squalene.
Follow-up research
This does not immediately make the sharks safe; more research is needed before these alternatives can definitively replace shark-produced squalene. “We need to further evaluate in preclinical studies their ability to protect against disease, as well as their safety,” said Fox. Larger-scale production of the substances is also a point of attention. “After that, we can also set up clinical research.” The substances are actually tested in humans, with the focus again on safety and immunogenicity (the ability to elicit an immune response).
Squalene cannot be extracted from sharks alone; it is also possible to extract it from plants. Plant-derived squalene works just as well as shark squalene. It is also no longer very unattractive from a cost perspective, MacDonald previously told Scientias.nl. “A 2010 study showed that plant-derived squalene was about three times more expensive than shark-derived squalene. But our data suggests that prices (…) have moved closer together and that the total price of shark-derived squalene and the price of plant-derived squalene is now quite comparable.” Nevertheless, it remains more attractive for many manufacturers to rely on sharks for the required squalene. Simply because it is much easier to extract squalene in large quantities from shark liver oil.
Optimism
While the 20 semi-synthetic versions of squalene that Fox and his colleagues have generated have yet to undergo extensive testing and so much work remains to be done, Fox is hopeful that vaccine makers will no longer depend on sharks in the future. He emphasizes that a squalene-like substance will probably remain indispensable for effective vaccines. “But we are hopeful that shark-derived squalene will become obsolete.” Because it can be gradually replaced by alternative substances, such as perhaps one of the 20 semi-synthetic alternatives that Fox and colleagues have now developed.
It would be very good news for the sharks, who are having a very hard time worldwide. “Shark populations are suffering from overfishing, and numbers of sharks and rays in the world’s oceans have declined by 71 percent since 1970,” Fox and colleagues write in their article. “A substitute for squalene that works just as well or better, but can be sourced sustainably, would be highly desirable and could alleviate pressure on shark populations.” But also with a view to public health, the search for an alternative to squalene is necessary. “(To, ed.) To be able to secure the future of this type of vaccine additions in the long term as well.”