One year ago, Minnesota was in the thick of its first wave of COVID-19 cases. New York had already been overwhelmed. People were still washing their groceries and quarantining their mail, and COVID-19 tests were just beginning to become more widely available.
Nobody knew when — or even if — a vaccine for this new virus would become available. In June of last year, the Food and Drug Administration said it was prepared to consider approving any vaccine that was found to be even 50 percent effective.
By the fall, news on the vaccine front was far better than that: Two vaccines — one developed by Pfizer and BioNTech, another by Moderna — were estimated to be around 95 percent effective. Soon, the FDA declared them safe and effective in emergency use authorizations, and the effort to vaccinate the population against COVID-19 began.
That high rate of success was particularly surprising since both vaccines relied on a technology that had been studied but never approved for use in a vaccine before: messenger RNA, or mRNA.
Now, scientists are thinking about how mRNA could potentially be used to treat and prevent diseases like Zika and the flu — maybe even cancer.
“I think basically this opened the floodgates and you’ll see lots of [mRNA] vaccines in the future,” said Richard Kennedy, who studies human immune response after vaccination at the Mayo Clinic.
Using mRNA
The way mRNA vaccines work is this: Through genetic sequencing, researchers identify the code associated with a particular protein in a targeted virus. They then create copies of that sequence — not the entire virus — to inject into the body via messenger RNA, the molecule that tells cells how to create specific proteins.
In the case of SARS-CoV-2, the coronavirus that causes COVID-19, the vaccines include mRNA with information from the virus’ spike protein, the mechanism by which it breaks into cells.
“It’s in the vial. Pull up the syringe and inject it into your arm, your muscle, and then it gets into the bloodstream,” said Louis Mansky, the director of the University of Minnesota’s Institute for Molecular Virology.
Once inside the cell, the mRNA tells cells to build the SARS-CoV-2 spike protein, then displays evidence of it on cells’ surfaces. When immune cells notice the foreign protein, they recognize it isn’t supposed to be there and can mount a response. If the immune system again encounters that spike protein, say, on the surface of a virus that has entered the body, it can recognize it and fight it.
An advantage of mRNA vaccines is they’re good at producing a strong immune response without requiring the injection of a live virus, said the Mayo Clinic’s Kennedy. Flu vaccines, by contrast, are made of inactivated or weakened virus, or virus particles. They help the body recognize the virus but don’t necessarily elicit a strong response.
Surprisingly effective vaccines
Last spring, though, it wasn’t clear that using mRNA to create a vaccine would work. Scientists developing the vaccines had to overcome obstacles that had previously plagued researchers trying to figure out how to treat and prevent diseases with mRNA. mRNA is fragile and hard to get into the cell, Kennedy said. Even if it does get into the cell, cells are good at recognizing and destroying it. That means for the mRNA vaccines to work, the mRNA had to get into cells and then be used to manufacture proteins rather than get destroyed right away.
Early news stories about the Moderna vaccine dismissed the company, Mansky said. The company was a relative newcomer whose business model was built around the idea of using mRNA to treat disease before COVID-19 came along. At the time, some of the other vaccine candidates, like the Johnson & Johnson vaccine, which uses the more traditional method of injecting a deactivated version of a virus to prompt an immune response, were considered more sure shots. (The J&J vaccine has, in fact, been found to be safe and effective by the FDA.)
“I remember so clearly last spring that the press were just dismissing Moderna — ‘Nobody’s heard about this kind of technology before and this is really new and you’re a really small company and you haven’t had anything [FDA]-approved before,’” Mansky said. Their vaccine was taken more seriously after Pfizer, a much bigger pharmaceutical company, and their partner BioNTech were advancing an mRNA vaccine, too.
“You really don’t know what’s going to not work and you don’t know what’s going to work,” Mansky said. “There’s always surprises — pleasant surprises, unpleasant surprises.”
As a virologist, Mansky said it was a pleasant surprise to him and many others in the scientific community that the mRNA vaccines worked, and so effectively.
With months of Minnesota’s first vaccinations, given to those most at risk and the people who care for them, COVID-19 cases and deaths in the state’s long-term care facilities had dropped by more than 95 percent.
Applications beyond COVID
Another advantage to mRNA vaccines is that they’re relatively easy to produce, Kennedy said.
Producing traditional flu vaccines requires a many-months process of growing its components in chicken eggs and requires scientists to predict which ever-changing flu strains are going to be prevalent in a given year months out. By contrast, mRNA vaccines can be manufactured relatively quickly if scientists know the sequence of the targeted viral protein.
“If you’re growing it in an egg, you need to make that decision four to six months ahead of time. RNA, maybe you can shorten that to one month,” Kennedy said. “You can make a logical guess, then you can wait and see. You can start producing the vaccines in August, say, and delivering them in September.”
If the strains were off, pharmaceutical companies could potentially know by October or November, then have an opportunity to produce a better vaccine before flu season is over.
Now that the technology’s been proven in the COVID-19 vaccine, scientists are thinking of all kinds of potential applications for it, including better vaccines for viruses like flu, malaria and tuberculosis and new vaccines for diseases like HIV and Zika.
The potential applications go beyond viruses. The cancer research field is increasingly interested in using the immune system itself to identify and deal with tumors, said Dr. Douglas Yee, director of Masonic Cancer Center and a professor at the University of Minnesota Medical School, in a talk this week.
Most cancers have a mutation in a specific gene, and “If you knew the sequence of that person’s tumor’s mutated gene, you could, I’m not going to say whip up a vaccine in a short period of time, but the technology is so much simpler to make these vaccines,” he said.
With the FDA’s emergency authorization of the mRNA COVID-19 vaccines, and all of the safety data that has come with the millions of vaccines administered, Yee sounded hopeful about advances in cancer care.
“Hopefully,” he said. “We’ll see these mRNA vaccines move forward in a cancer therapy.”
Early on there was some talk of mRNA vaccines for the common cold. That would certainly be worth pursuing.