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- Research , Home Stretch
- 14/07/2021
Home Stretch | Smarter vaccine packaging
The corona pandemic has been responsible for the breakthrough of mRNA vaccines, in which a genetic instruction is administered in a sac made of fat, technically known as a lipid vesicle. According to Pascal Welzen, a polymer sac should also work - and possibly even better. Having started his school career in secondary vocational education, he last week gained his doctorate in Bio-Organic Chemistry.
That his research would now be so topical was something Pascal Welzen could not have foreseen when he started his doctoral studies four years ago in Nijmegen under Jan van Hest, now Spinoza laureate and TU/e professor. But it is gratifying, despite the bitter reason why vaccines are now earning such attention. “This doctoral position was a deliberate choice, precisely because the research had such strong potential for applications.”
This held appeal because for years this late bloomer had sworn he would never do a PhD, which he eventually came to after studying at an applied university. After rising through the various vocational streams, he completed vocational higher education. “Doctoral candidates were nerds in my eyes, working all day long on a detail that was never going to benefit society. But this was a really practical project, in cooperation with pharmaceutical companies such as GSK and Zoetis and the department of Pediatric Infectious Diseases at Radboudumc.”
Nano sac
Welzen's research is all about 'polymersomes', a kind of nano sac made of bioplastic degradable by the body. He explains that while these are a hot topic of study as vehicles for the controlled release of medicines in the body, as a transport medium for the latest generation of vaccines they still have a low profile. Even though, in principle, polymersomes are more robust and versatile than the lipid vesicles in which mRNA is locked in the highly successful vaccines produced by Pfizer/BioNTech and Moderna.
These fragile vaccines need very cold storage, he continues, while polymersomes will stay good for months if kept in a refrigerator and even in a freeze-dried state. “This is important if you want to produce cheap vaccines for poorer countries. For this market you also want to get a good result with as little vaccine as possible, because mRNA is expensive.”
Exterior
What's more, mRNA is not the only thing you can lock into a polymersome; these plastic sacs open the way for producing other types of vaccines. “We can make them so that an antigen (a molecule recognized by the immune system as a threat, ed.) can easily be clicked onto their exterior,” says Welzen. In this way, you mimic the pathogen without causing its adverse effects, he explains.
He has also demonstrated that it is relatively easy to modify the polymersomes so that they are stable in neutral acidity (such as in the blood), but fall apart in a more acidic environment (such as when they are taken up into the body's cells). “The reverse is also possible,” this native of Limburg points out. “We have also produced polymersomes that fall apart in the neutral acidity of the intestines yet are able to survive the stomach's acid environment.”
Such polymersomes could form the basis of a vaccine - or medicine - that you simply drink, he explains. But initially they are working towards a vaccine in the form of a nose spray as opposed to an injectable liquid. “A nose spray is less invasive and it doesn't require needles, another factor in its favor in poorer countries. And because most diseases penetrate the body via the nose, this is the logical place to generate strong local immunity.”
Activate
In principle, the polymersomes Welzen has produced are inert, he tells. “They are administered and the body does absolutely nothing with them. But for an effective vaccine, the immune system must be activated to the right degree. And so, on the polymersomes I have hung a piece of synthetic DNA that the body recognizes as alien.” And to lure the right immune cells, he also attached to the polymersome a fragment of an existing antibody: a protein produced by the body to recognize and neutralize certain pathogens. “In blood samples this combination proved very effective,” Welzen says.
The step that should have been the apotheosis of his research - combining all the individual features of the polymersomes into a single prototype vaccine - has unfortunately been denied Welzen. “We still hope to secure funding for this follow-up research.”
Meanwhile he has started work as a postdoc in Van Hest's group, tackling a very different project: “We aim to develop a medicine for blindness in old age. At some point, I would really like to continue working on vaccines, but I have to say that my current project is also fascinating.” Perhaps he has become more of a science nerd that he would have thought possible.
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