The Scientist Using Rabies Vaccine Secrets to Halt Coronavirus
WHY YOU SHOULD CARE
Because her technology could be the ticket to a faster mass-produced vaccine.
By Nick Fouriezos
When Mariola Fotin-Mleczek moved from her native Poland to southwest Germany in the early 1990s, the plan was for the 27-year-old to continue her psychology studies while her husband took a teaching position at the University of Stuttgart. It was only after arriving that she discovered the university didn’t offer any courses in psychology. So she shifted to biology, with an emphasis on the burgeoning technologies that utilized computers and the then-nascent internet to bring about stunning discoveries over the next three decades.
When all is said and done, the world may end up being very thankful for the scientist’s chance career switch. That’s because Fotin-Mleczek and the company CureVac have emerged as one of the most promising avenues in the search for a COVID-19 vaccine. While there are a number of solutions in progress, the CureVac model stands out because its delivery mechanism is messenger RNA (mRNA) — a relatively novel scientific use for the genetic molecule that Fotin-Mleczek specializes in, having published more than 30 peer-reviewed studies on the subject and owning several patents.
“Nature has invented mechanisms to activate our immune system against infectious diseases,” says Fotin-Mleczek, now 53 and CureVac’s chief technology officer. “With our unique messenger RNA technology, we mimic nature and give our body the information how to fight against the virus.”
The biggest advantage mRNA has is that it can treat patients with just a fraction of the dosage that other vaccines may require.
There are a number of reasons why using mRNA could be so promising for a coronavirus cure. While scientists using traditional vaccines have to craft a tailored delivery mechanism for each disease from the ground up, mRNA relies on four molecular building blocks that don’t change from virus to virus. That should allow CureVac to move faster in developing a workable vaccine, particularly because the company has already proved its model doesn’t have adverse effects for humans.
The biggest advantage mRNA has, though, is that it can treat patients with just a fraction of the dosage that other vaccines may require. CureVac’s rabies vaccine, fueled by its use of mRNA, was recently shown to fully protect humans with two doses of only 1 microgram (one millionth of a gram). If a similarly small dosage can be used to vaccinate coronavirus patients, it would help solve one of the biggest supply chain challenges in human history — even when there is a vaccine, how do you supply a global population of nearly 8 billion?
CureVac has already conducted testing that confirmed the rabies infection and response results could be translated to a coronavirus-focused mechanism. “The data is very encouraging. It supports the idea that the infection is what we suspected,” Fotin-Mleczek says. The next obstacle: While scientists “can be sure that the antibodies we induce are the right ones to fight the virus,” she says, “the challenge is what level is needed to provide protection?” In short, determining the dosages that help each type of patient the most.
Such clinical trials will likely start next month and take most of the summer. “We think in autumn, as in September, we will have a very good data basis to get approved” by government regulatory bodies, she says, although how long it takes to actually get the vaccine onto shelves will depend on how fast regulators move. There are reportedly at least six vaccine candidates leading the race so far, including ones from Moderna Therapeutics and Pfizer in the United States, Beijing-based Sinovac Biotech and Oxford University in the United Kingdom. Most have either begun, or will soon begin, human clinical trials.
There is reason to believe a CureVac solution could be approved faster than other vaccines. Since the delivery mechanism has already been proved safe (and scientists are starting to see in patients the effects of low doses of coronavirus), there seems to be less of a chance for adverse side effects. The model is so replicable it could even be used as a vaccine to treat other pathogens at the same time — imagine a single shot to fight both influenza and the coronavirus.
Other companies have extolled the promises of mRNA, without breakthrough results. Most notably, Moderna has seen its stock rise exponentially, fueled by an injection of $500 million in U.S. government funds to find a coronavirus cure.
But the scientific challenges remain stark: When mRNA is introduced, the body typically shuts down protein production, a problem when the formation of proteins to fight viruses is the whole point of a vaccine. And, as Ryan Cross, associate editor of Chemical Engineering and News magazine, wrote in 2018, “even if the molecule makes it into the cell — another challenge that has long vexed drug delivery experts — the mRNA might not make enough protein to actually be useful.” To date, none of Moderna’s products have gone to final phases of clinical trials, received Food and Drug Administration approval or gone to market. CureVac has yet to bring a product to market either, despite having formed in 2000.
Still, that isn’t abnormal for biotech startups, which often have long runways before breakthroughs, and CureVac has received investments from the Bill & Melinda Gates Foundation and partnered with everyone from Eli Lilly to CRISPR Therapeutics. Since Fotin-Mleczek became employee No. 20 in 2006, CureVac has grown to around 470 employees in three offices: Frankfurt; Tübingen, Germany; and Boston, the center of the biotech industry. And, as CureVac Director of Communications Thorsten Schüller says, developing the coronavirus vaccine would be the proof of concept that mRNA-focused startups need to show that “our technology works and could relatively easily apply to other therapeutic areas.”
The pandemic could also serve as Fotin-Mleczek’s coming-out party, given her central role in mRNA research. When she first switched careers, her urgency was partly motivated because she knew her growing family — she has three children, two of whom are now adults — would demand much of her attention. But the nature lover quickly became fascinated with the science of how cells get activated, and why. “It was all about the decision processes in cells, conversations about life and death,” she says. Now, nearly three decades later, her role in those conversations could carry implications not just on a molecular level but also on a global one.