Will mRNA Flu Vaccines Be Better Than the Current Flu Shots?

Photo credit: Inthon Maitrisamphan / EyeEm - Getty Images
Photo credit: Inthon Maitrisamphan / EyeEm - Getty Images

MRNA vaccines broke onto the global stage this year as the technology behind some of the most highly effective COVID-19 vaccines. But mRNA technology isn’t new—it has been around for years and just never found the right application.

Given how successful the mRNA Pfizer-BioNTech and Moderna COVID-19 vaccines have been, several companies are looking into using the technology to make a newer type of flu vaccine.

Pfizer announced that they are again partnering up with BioNTech to work on a “better” flu vaccine using mRNA technology. “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,” Pfizer said in a press release.

Now, Pfizer, Moderna, and Sanofi are in phase I clinical trials for mRNA flu vaccines, with several other companies planning to do the same.

But why is an mRNA flu vaccine needed, and could it potentially do better than our existing flu vaccines? Here’s what you need to know.

How our current flu vaccines work

The flu vaccine process starts with a group of researchers analyzing data to try to determine at least six months in advance which strains of the flu will be most dominant for the coming flu season, explains Thomas Russo, M.D., professor and chief of infectious disease at the University at Buffalo in New York.

The Food and Drug Administration (FDA) has approved three different flu vaccine production methods in the U.S.—egg-based, cell-based, and recombinant.

Most flu vaccines used in the U.S. are egg-based. The process starts with the Centers for Disease Control and Prevention (CDC) giving vaccine manufacturers candidate vaccine viruses (CVVs) that have been grown in eggs. Those CVVs are then injected into fertilized hen’s eggs and incubated for a few days to give the viruses a chance to replicate, i.e. make copies of themselves. The liquid is then removed from the eggs and the virus is either killed (for inactivated flu viruses, which is what the flu shots are) or weakened (if the manufacturer is making the flu nasal spray). From there, the antigen is purified, tested, packaged, and distributed.

Cell-based flu shots work slightly differently. The CDC gives manufacturers CVVs that have been grown in cells. Those CVVs are put into cells taken from mammals and given time to replicate. The fluid is then collected, purified, packaged, and processed.

The recombinant flu vaccine is created with a gene that provides cells with genetic instructions for making a surface protein found on flu viruses called hemagglutinin (HA). That antigen that triggers your immune system to make antibodies to fight the flu.

The gene for making the antigen is combined with a baculovirus, a type of insect virus that doesn’t make people sick. The baculovirus then helps get the genetic instructions for making the flu virus HA antigen into the cells in the host cell line, and it starts making the HA antigen. After that, it’s grown, collected, purified, and packaged.

The flu vaccines take six months to create, making this a lengthy process.

How effective are our current flu vaccines?

Current flu vaccines are hit or miss, and their efficacy falls way short of those of the mRNA COVID-19 vaccines. The CDC has data on the efficacy of several past flu vaccines, and it ranges from as low as 10% to as high as 60%. (The Pfizer-BioNTech COVID-19 vaccine, by comparison, has an efficacy of 95%.)

“The efficacy of our flu vaccines is less than excellent,” Dr. Russo says. “Part of it is the long production time in terms of guessing what will be circulating. Sometimes we guess wrong.”

What do doctors think about the possibility of mRNA flu vaccines?

They’re in favor of it. “Because the speed of the development of an mRNA vaccine is considerably faster than the current flu vaccine production techniques, an mRNA vaccine may allow decisions about what strains to include to be made later and result in a better matched vaccine, says infectious disease expert Amesh A. Adalja, M.D., a senior scholar at the Johns Hopkins Center for Health Security.

Dr. Adalja points out that many of the currently-used vaccines use a technique from the 1940s, which requires a “long lead time” for selecting flu strains. “It is also the case that mRNA flu vaccines may have higher efficacy and protection against all infection as opposed to current vaccines, whose benefit is primarily against severe disease,” Dr. Adalja says.

Dr. Russo cites the high efficacy of the mRNA COVID-19 vaccines as “promising” for mRNA flu vaccines. “It holds the promise that mRNA technology could do the same for flu vaccines,” he says.

But William Schaffner, M.D., an infectious disease specialist and professor at the Vanderbilt University School of Medicine, says a lot needs to happen between now and when mRNA flu vaccines could make it to the masses. “Obviously, mRNA technology is appealing to create a better flu vaccine,” he says. “But, if we had a candidate mRNA flu vaccine, what would all of us and particularly the FDA require before they have a license to this?” The vaccine would have to be proven to be effective and safe, he says, and under a non-pandemic situation, that can take time.

There has been a lot of chatter about new mRNA flu vaccines being ready as early as next year, but Dr. Schaffner says that doesn’t necessarily mean that they’ll be available for the masses to use.

“In the past, development of new influenza vaccines has taken several years,” Dr. Schaffner says. While the mRNA COVID-19 vaccines were fast-tracked by the FDA’s emergency use authorization status due to the pandemic, he’s doubtful that the same would apply to a new mRNA flu vaccine. “I think it will take several years at best before we have new, licensed and defined mRNA flu vaccine. It’s not going to happen quickly,” Dr. Schaffner says.


This article is accurate as of press time. However, as the COVID-19 pandemic rapidly evolves and the scientific community’s understanding of the novel coronavirus develops, some of the information may have changed since it was last updated. While we aim to keep all of our stories up to date, please visit online resources provided by the CDC, WHO, and your local public health department to stay informed on the latest news. Always talk to your doctor for professional medical advice.


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