Is mRNA The Future Of Flu Shots?

A new mRNA vaccine against the flu has proven itself more effective than existing vaccines in a new clinical trial. The Pfizer-developed vaccine was found to be 34.5 percent more effective than current vaccines at preventing illness caused by influenza A in a trial of over 18,000 people. Though the new vaccine was associated with more side effects, severe adverse events were uncommon regardless of which vaccine people received.

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mRNA vaccines: A refresher

mRNA vaccines came to prominence during the COVID-19 pandemic, but part of the reason the Pfizer/BioNTech and Moderna shots were developed so quickly is that this technology had already been under investigation for some time. Its creators even bagged a Nobel Prize. 

They work differently from other, more traditional vaccines, so it’s worth reminding ourselves of what they are.

mRNA stands for messenger RNA, small molecules of nucleic acid that your cells are making all the time as they work to produce all the proteins you need to live. The mRNA included in vaccines can be thought of as a recipe or instruction manual for a specific protein. 

Once injected, the mRNA is taken up by cells and “read” in the same way as the mRNAs you naturally produce. The COVID-19 vaccines, for example, include mRNA encoding the virus’s spike protein. 

In this way, mRNA vaccines temporarily coopt normal cells and turn them into protein factories, churning out copies of a virus protein so that the immune system can learn to recognize and react to it. This is the goal of any type of vaccine: building a robust immune response without the danger of having to actually catch the disease in question. 

mRNA doesn’t last forever, so it can’t cause any permanent changes to human cells. It also cannot get inside the nucleus, where your own DNA is stored, so it cannot make any changes to the genome. These facts are often misunderstood or misrepresented by those who oppose the use of these vaccines. 

A study from the University of Pennsylvania’s Annenberg Public Policy Center, published just this week, looked at ways of tackling misconceptions about mRNA vaccines. In two experiments featuring 1,540 and 2,038 participants, respectively, researchers tested whether graphics, animations, and clear explanations could help blunt the impact of misinformation about DNA changes.

The models either explained in detail how mRNA vaccines work or demonstrated the defenses human cells have against foreign DNA.

The models worked both preemptively and as a rebuttal to misleading claims. “We found that respondents who saw the problematic claims along with the mental models were more likely to answer questions in an evidence-based manner than those seeing the problematic claims alone,” said team lead Kathleen Hall Jamieson in a statement. 

The effect was slightly better when the participants were forearmed with an understanding of mRNA vaccines before hearing the misinformation. Which hopefully, after reading all of the above, you now are too!

How does the new flu vaccine differ from previous vaccines?

The latest flu vaccine that’s being trialed is more correctly known as a “modRNA” vaccine. 

As Professor Paul Griffin, an infectious disease expert at the University of Queensland School of Medicine, explained to the Science Media Centre (SMC), in modRNA vaccines, “components of the mRNA (nucleosides) are replaced by naturally occurring modified nucleosides (including pseudouridine for example). This improves performance, including being translated more efficiently.”

This is a whole different setup from the flu shots you can go and get right now from your local pharmacy.

Seasonal influenza vaccines in use today are primarily inactivated trivalent vaccines, meaning they contain inactivated versions of three different flu virus strains. Some quadrivalent vaccines, with four strains, are also available.

Because they’re inactivated, it’s not possible to develop an active flu infection from the shot itself. You can catch flu in the wild immediately before or after your shot – it takes about two weeks to reach the maximum protection – or develop flu-like symptoms from exposure to another virus.

As with any vaccine, though, side effects can happen. Serious or life-threatening side effects are very rare, something that was borne out in the clinical trial of the new modRNA vaccine too.

There are other types of flu vaccines on the market. In some places, children are offered a nasal spray instead of an injection. This is generally a live vaccine, so the flu viruses contained within it have been weakened but not totally inactivated.

Nasal spray vaccines provoke an immune response in the mucosal tissues inside the nose and respiratory tract – particularly useful when you’re dealing with a virus that is spread through the air, as this is how it most often enters the body.

The trial results in detail

“In a large, global Phase 3 trial involving over 18,000 healthy adults (aged 18-64), the mRNA vaccine demonstrated a 34.5 percent higher relative efficacy at preventing lab-confirmed flu compared to a licensed inactivated vaccine (Fluzone),” explained Associate Professor Vinod Balasubramaniam, a molecular virologist from Monash University in Malaysia, to the SMC.

Most of this positive impact was driven by a strong immune response against influenza A viruses, specifically H1N1 and H3N2. Influenza A is responsible for most seasonal flu disease in humans and tends to cause more severe outbreaks.

However, the new vaccine was more likely to cause side effects like fevers, though these were unlikely to be serious. It also did not perform as strongly against influenza B.

Balasubramaniam added that “the vaccine induced a weaker antibody response against influenza B strains. While there was too little flu B circulating during the trial to measure real-world effectiveness, this is a noted weakness.”

Another weakness that was pointed out was the lack of inclusion of an over-65s age group in the trial, as older adults are particularly prone to more serious complications from flu. As Balasubramaniam said, “This is a promising step forward but not a complete solution for all.”

No vaccine is 100 percent effective, and flu vaccines come with the additional challenge of having to predict which strains will be the most prevalent well in advance of the season. Until we have a universal vaccine – something many scientists are actively working on – this will continue to be a problem.

The authors of the trial note that US-licensed vaccines in the 2022-23 season had an effectiveness of approximately 44 to 54 percent in those aged 64 and under, whereas the modRNA vaccine would have reached around 60 to 67 percent.

That could make a notable difference during a flu season like 2024-25, which was particularly severe and saw the most children dying from flu in the US since the swine flu pandemic. With the arrival of a mutated H3N2 strain called subclade K, there are fears this year’s season could be a bad one as well. Any improvements we can make to vaccines of the future will be welcomed.

The clinical trial is published in the New England Journal of Medicine. The study on mRNA vaccine misconceptions is published in PNAS.