The how and why of a universal flu vaccine

By Shauna Bennett

A new school year has started, crispness is returning to the night air, the maple leaves are reddening, and everything is pumpkin spiced. This can only mean… flu season is coming.

The influenza (flu) virus is associated with thousands of deaths and hundreds of thousands of hospitalizations each year, and flu season has become synonymous with the winter months. The best way to combat flu infections is the vaccine offered each fall. The seasonal flu vaccine has its limitations, however, due to its extensive development process.

What would it take to make a vaccine that doesn’t need to be revamped every year? Scientists are getting close to an answer, but it’s easier said than done.

The flu virus

The flu virus mutates rapidly compared to other viruses we are vaccinated against, bringing the need for new vaccines every year. In general, when a virus enters our body, our immune system recognizes it as an invader and makes antibodies based on the virus’s shape. These antibodies are designed to stick to the outside of the virus particle, thus preventing it from entering the body’s cells to cause infection.

When the virus mutates, however, these mutations can lead to small changes on the surface of the virus particle. The surface of the new mutated virus particle has a slightly different shape, so it can escape from the previous antibodies that were made and sneak into cells. Once inside cells, the virus makes copies of itself, and those copies leave to enter nearby cells (or nearby humans when expelled through a cough or a sneeze).

fluvirus
Diagram of flu virus. Image credit: CDC.gov, Dan Higgins

The current flu vaccine

The quickly-mutating nature of the flu virus means that we need new vaccines each year to keep up. However, it is time-consuming and complicated to produce an effective vaccine.

The yearly flu vaccine is based on three or four types of flu that are predicted to be the most widespread strains for the northern hemisphere that year. World Health Organization (WHO) specialists gather each February to decide which strains to use by tracking flu infections that have been circulating throughout the world. The FDA makes the final decision of which viruses to use for the US vaccine. Vaccine manufacturing companies then work on growing large quantities of those strains and inactivating them for use in the vaccine.

After selecting the strains to include, it takes 6 – 8 months before the vaccine is ready for the public. If a pandemic flu virus arises that is too different from what previous vaccinations protect against, this lengthy production process means it would take too long to create a new vaccine to prevent widespread flu-associated deaths.

The promise of a universal vaccine

Because there are so many flu strains and the flu virus mutates so quickly, the idea of a “universal” vaccine is highly desirable. A universal vaccine would protect against any strain of flu (or type, like H1N1 vs. H5N1) and thus would not need to be updated every year, alleviating the time and effort of vaccine production and dissemination and increasing the fraction of the population that is protected.

As mentioned earlier, when the immune system recognizes a virus it makes antibodies that match the outer physical features. The current vaccine delivers inactivated virus particles (that cannot make copies) so that a person’s immune system will make antibodies in advance of encountering a live virus.

The physical features recognized by antibodies include a mushroom-shaped protein called hemagglutinin (HA) that protrudes from the virus (blue in the diagram). Antibodies recognize the head of the mushroom, but this part of the protein changes most through mutations.

However, scientists found that the stem part of the mushroom-shaped HA protein does not mutate like the head part. If we could get antibodies to target this part of the virus, they could protect against many different flu strains.

 

 

A universal vaccine on the horizon

 Recent studies, published in Science and Nature Medicine, have shown promise towards developing such a vaccine based on the stem of the HA protein.

 This type of vaccine would work by introducing a modified version of the HA protein made of only the stem portion, allowing antibodies to be made exclusively against the stem. Then, theoretically, antibodies would exist in the body that could recognize almost any type of flu virus that comes along.

The construction of a stem-only HA protein was not a simple process, but two research groups have managed to produce it and test it using mice.

They injected mice with the protein, waited until antibodies were made, and then infected the mice with flu virus. To the researcher’s delight, the mice that were vaccinated survived infection, which is only the case when vaccination is successful. Additionally, the vaccinated mice were protected against multiple flu types, showing broad protection. Trials with monkeys also showed promise; flu symptoms were less severe in vaccinated compared to unvaccinated monkeys.

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Flu vaccine. Image credit: Jim Gathany, CDC.gov

These developments are exciting for the scientific community, but mice and humans have very different immune systems. The sign of some protection in monkeys is promising, but it needs to be validated before clinical trials can be conducted on people.

Dr. Barney Graham of the National Institute of Health, one of the authors of the Nature Medicine paper, told the Huffington Post, “It’s not that we have something that’s going to be in a bottle next year. I don’t want people to get that impression. But it is exciting, because it does put us on this path that could lead to something.”

For now, you’ll still have to remember to get your seasonal vaccine.

 

 

About the author

shaunaShauna got her PhD at the University of Michigan in early 2014 in Cellular and Molecular Biology and is currently living in Southern California pursuing new opportunities. She studied small DNA tumor viruses for about seven years and thinks they are really neat. Before that she studied mouse genetics at the NIH and chemistry at Bryn Mawr College. She never really could decide on which scientific subject was the coolest, so she is now hoping to establish a career where she can read and write and talk about all science subjects all the time. In her free time she likes drawing and attempting martial arts. She also likes to help people, so she started the blog PhD Over Easy with her former grad school baymate Nicole Broekema, where they profile non-academic career paths. You can follow her on Twitter or check out her blog, Membrane Penetration.

Read all posts by Shauna here.

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