How Pfizer Shows the Promise Of Gene-Based Vaccines

Until now, this approach has been largely experimental. If Pfizer/BioNtech's vaccine works as well as early indications suggest it might, use of gene-based therapies could expand exponentially, with beneficial results across a variety of illnesses. JL

Nicole Wetsman reports in The Verge:

Pfizer and BioNTech’s vaccine is made from genetic material called mRNA (which) carries instructions inside of cells and tells them to build proteins. The vaccine includes a specific piece of mRNA that contains instructions for how to make the spike protein of the coronavirus, which is the tiny bit that lets it bind to human cells. The vaccine spurs the human body to make copies of that protein. When the immune system encounters those spikes, it learns to recognize and block them.

Pfizer and BioNTech announced this week that their vaccine was 90 percent effective at preventing symptomatic COVID-19 in clinical trials. The data is still preliminary and hasn’t been examined by independent researchers, but it’s good news for both this specific vaccine and for the other coronavirus vaccines in the pipeline — especially the ones that are based on the same genetic technology.

“It’s extremely encouraging, in my view, not only for the Pfizer vaccine, but broadly speaking for the platform,” says Ross Kedl, an immunologist at the University of Colorado.

Pfizer and BioNTech’s vaccine is made from genetic material called mRNA. mRNA carries instructions inside of cells and tells them to build proteins. The vaccine includes a specific piece of mRNA that contains instructions for how to make the spike protein of the coronavirus, which is the tiny bit that lets it bind to human cells. The vaccine spurs the human body to make copies of that protein. When the immune system encounters those spikes, it learns to recognize and block them.

Gene-based vaccines are relatively simple to develop and manufacture. For years, they’ve been heralded as the future of vaccine development. However, until now, they’ve been largely experimental. The Food and Drug Administration (FDA) has never approved one for use in humans. Rosemary Rochford, also an immunologist at the University of Colorado, says she was initially skeptical they’d work as well as some other types of vaccines, like ones made from inactivated viruses. But the Pfizer data — assuming it holds up on further evaluation from outside experts and the FDA — is a strong proof of concept. “This mRNA platform seems to be very promising,” she says.

The Moderna vaccine candidate, which should release initial data soon, is also based on mRNA. “I would assume their efficacy is probably going to be similar,” says Drew Weissman, the University of Pennsylvania immunologist who conducted the research behind mRNA vaccines. He’s also an advisor for BioNTech, the company that partnered with Pfizer on this vaccine.

Moderna and Pfizer / BioNTech also had equivalent results in their phase 1 and phase 2 clinical trials, which are smaller scale, Kedl says. “You could almost superimpose the two, or switch the names and you would fool everybody. They really both are really strongly supportive of each other in terms of the strength of the immunity.”

Before the COVID-19 pandemic, there wasn’t much research done on gene-based vaccines for infectious diseases — a lot of the work focused on treating cancers, not viruses, Rochford says. Clearance of the first gene-based vaccine for something like COVID-19 would open a new world of options for vaccine developers.

Pfizer’s vaccine hasn’t been authorized or approved by the FDA yet, and there are still a few steps before it reaches that point. The data released this week, though, points in that direction.

“I think it’s a game changer,” Kedl says. “I wouldn’t be surprised if, in the next 10 years, we see this work its way into the flu vaccine.”

Once these vaccines cross the initial hurdle of proving to be effective and safe, researchers can start to study them more intensely. “Once we know it works, we’ll take some time to go find out why,” Kedl says.

Rochford says she’ll be watching to see how long the immunity provided by these mRNA vaccines sticks around, and how long the antibody response the vaccine generates lasts. Research shows that, for people who catch COVID-19 and produce their own natural antibodies, the levels dip before leveling out. But vaccine-generated antibodies are different. “Your body is not fighting an infection and a whole disease process,” she says. “I’m more confident that the durability will be better than what we see in a natural infection.”

Companies and researchers will also be on the lookout for ways to improve the vaccines. Based on early reports, they cause more achiness and other mild side effects than other vaccines, for example. “There may be some modifications, we may start shifting some things,” Kedl says.

One downside to mRNA vaccines is that they have to be stored an an extremely low temperature, which makes them more difficult to transport. mRNA is an unstable compound, and keeping it cold makes sure it won’t break down before its injected into the arm of a patient. Weissman says that teams at pharmaceutical companies are working on ways to keep these vaccines stable at higher temperatures, and he thinks that future generations of the COVID-19 vaccines will be able to stay in refrigerators. Weissman is also working on a way to freeze-dry the genetic material, so that vaccines can be stored at room temperature. “I don’t think that’s going to be a big thing to worry about,” he says.

Having another proven way to make vaccines will help researchers prepare for the next pandemic. There isn’t anything unique about this specific coronavirus that makes mRNA vaccines work well — the platform could be just as effective for other viruses. “Say we have a new coronavirus, or a new Ebola virus, or new emerging pathogen,” Rochford says. “It’d be fairly easy to generate these once you have the sequence and some basic biology. Moving forward, it gives us a very strong platform for a rapid response.”