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New RNA Technology Could Get the Flu Vaccine Right, Every Year

New RNA Technology Could Get the Flu Vaccine Right, Every Year
OUR SCIENCE/ New RNA Technology Could Get the Flu Vaccine Right, Every Year
November 30, 2018

We’ve been making the flu vaccine in nearly the same way for 70 years. A new technology based on RNA could disrupt that.

Developing the flu vaccine each year is like a game of prediction.

Scientists must peer into a “crystal ball” of viral surveillance data and make their best forecast of which viruses will be dominant the next season. Since it takes nearly six months to make enough vaccine, these early picks can be poor matches. Consider that even in a good year, the flu vaccine is only about 60 percent effective at preventing illness.

But Pfizer has recently entered into a collaboration with German biotech BioNTech to develop new RNA vaccine technology to create a better flu shot. The multi-year partnership will build upon BioNTech’s RNA technology and could significantly speed up the vaccine manufacturing process, removing much of the guess work of matching the right formulation to the season’s dominant strains.

“It always a bit of lottery each year when the flu vaccine comes out. There’s always concern whether they’re will be enough supply in time for the peak season and how well it’s going to work,” says Phil Dormitzer, Vice President and Chief Scientific Officer, Viral Vaccines at Pfizer’s Pearl River, N.Y. research site. “If we are able to reduce or eliminate the mismatch we have from year to year, it would be a huge opportunity to help prevent influenza illness and death.”

Removing the guesswork

With conventional vaccines, the flu virus is grown in chicken eggs or mammalian cells, and then inactivated and processed to be made into vaccines. The disadvantage to this approach is there is much variability in the finished product — the virus can mutate even during vaccine production — and the production process must be updated for every new strain.

But with this new technology, scientists would not need to use live cells in the lab. Instead, they would monitor surveillance data on the current viral strains and use information on the genes of those strains to synthetically produce corresponding RNA. When a person is injected with the RNA, their own muscle cells would turn into vaccine “factories,” creating proteins that stimulate the immune response. “We predict that their cells will gobble up the RNA and start expressing the flu antigen,” says Dormitzer. Because this approach more closely mimics what happens when a person is infected with the actual flu (but without the person becoming sick), a stronger immune response will hopefully be elicited. “You get more arms of the immune system involved,” adds Dormitzer, referring to aspects of immunity that involve both antibody and T-cell activity.

Rapid response

The manufacturing process for the RNA vaccine is also simpler that the current vaccine technology. At research scale, an RNA vaccine can be made eight days after the sequence of a new flu virus is first known. The equipment used to make the vaccine bulk could fit in a shipping container. “Experts predict that the vaccine could be made quickly, such that you can pick your strains closer to the actual flu season removing a lot of the guesswork required with the current technology,” says Dormitzer. “Unlike in conventional flu vaccine manufacturing, even if the flu strains change from year to year, the production process remains the same.”

It also gives scientists and public health officials better tools to rapidly respond to major flu outbreaks or pandemics. “You can even consider making rescue vaccines,” says Dormitzer. “In many cases, if we did get the strains wrong a new vaccine could be rapidly produced to specifically address the strain causing the outbreak.”

The technology is several years away from being tested in the U.S., but Dormitzer is optimistic about the potential of this new approach. “It’s technology that has the capacity to disrupt and greatly improve influenza vaccination,” he says. “If successful, it could supplant a lot of the way we do things now.”

"If we are able to reduce or eliminate the mismatch we have from year to year, it would be a huge opportunity to help prevent influenza illness and death." - Phil Dormitzer

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