How do you make a universal flu vaccine? A microbiologist explains the challenges, and how mRNA could offer a promising solution

To everything there is a season, and for the flu, it’s wintertime. Flu cases peak between December and February, and the flu vaccine is your best defense. Getting the vaccine means you will be less sick even if you get a breakthrough infection.

However, your immune system is in a constant race against the flu virus. Like the virus that causes COVID-19, influenza rapidly changes and mutates into new variants, so manufacturers have to update the flu shot to try to keep pace. After identifying a new flu variant, it takes manufacturers about six months to update the vaccine – and in the meantime the virus can mutate again. This phenomenon is called antigenic drift, and can reduce the effectiveness of the flu vaccine for that season.

An ongoing threat is that a major change in the flu virus, or antigenic shift, could cause the next flu pandemic. This happens when a flu virus from animals, such as birds or swine, gains the ability to transmit between humans. Most people will have no immunity against this new animal-origin virus, so it could quickly spread into a pandemic. If that happens, the annual flu shot will not be effective and can’t be updated fast enough to stop a global spread.

I am a researcher developing new vaccines to prevent future pandemics. Nearly 20 years ago, my lab and several others developed a vision of building a universal influenza vaccine that could give us the leading edge in the race against influenza and prevent the next flu pandemic by effectively combating any eventual flu strain. One potential way to do this is with messenger RNA, or mRNA.

A primary challenge in developing vaccines against influenza is how rapidly the virus mutates.

What is a universal influenza vaccine?

A universal influenza vaccine is one that does not need to be updated each year because it is designed to protect against all or most influenza variants. Scientists are exploring several ways to develop universal influenza vaccines. Most fall into one of two buckets.

The first includes vaccines that focus on conserved, or unchanging, parts of the virus. This strategy directs the immune system against parts of the virus, or antigens, that are shared among all variants and can’t mutate without weakening or killing the virus.

The second includes mosaic vaccines. These are like a cocktail of protein pieces taken from different variants. The blend is made up of versions of the protein hemagglutinin – essential to the influenza virus’s ability to infect cells – that is found in all flu variants circulating in animals and people. The goal is to induce immunity against nearly all variants so there will be fewer gaps in the immune system’s defenses for the virus to slip through.

Using mRNA for a universal flu vaccine

The recent success of mRNA vaccines for COVID-19 shows promise for their use in achieving the vision of an effective universal influenza vaccine….

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