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The Holy Grail of influenza research: a universal flu vaccine

Creating the universal flu vaccine will require more than innovation in science. Joel Kramer

Facts about Flu - What if you needed just one flu shot to protect you from pandemic as well as the yearly seasonal flu viruses in circulation?

Imagine you could only identify people by their jackets. Once someone took off their jacket and put a new one on, you would have no idea who they were. Sound frustrating?

No, this is not a pitch for a new sci-fi movie – it’s how your immune system and the influenza virus interact.

Your immune system uses clues from intruders, such as viruses and bacteria, to figure out how to respond (or not respond). In the case of influenza, the clues most easily and quickly available are the outer coat proteins of the virus, which are dominated by two called hemagglutinin (HA) and neuraminidase (NA).

Unfortunately, these proteins change or mutate more often than do other influenza proteins. This means that every time your body encounters an influenza virus with slightly different coat proteins, it can’t immediately recognise the virus.

And, in the worst-case scenario, this means you will get ill before your immune system can work out what happened and mount a defence.

These mutations in viral coat proteins are the main reason influenza vaccine formulations are changed frequently and vaccination is recommended every year.

Better targets

The idea behind a “universal” influenza vaccine is to devise a way of educating your immune system to be less easily fooled by small changes in the virus’ coat. Ideally, a universal vaccine would protect you from all types of influenza viruses for a lifetime.

Two main types of influenza infect humans, type A and type B (seasonal influenza vaccines comprise both types). They’re quite different and likely require different vaccine strategies.

Influenza A is more complex, being further subdivided into subtypes based on their reactivity in specific tests (called antigenicity) and the genetic similarity of their hemagglutinin and neuraminidase.

Two examples of A strains are 2009 H1N1 pandemic influenza and the H7N9 strain currently infecting people in China.

In the short term, it’s likely that when someone talks about a universal influenza vaccine, she’s really talking about a more broadly cross-protective vaccine against more than one strain of influenza A.

Our immune system identifies influenza viruses by their coats. Guy H/Flickr

A broadly cross-protective vaccine would be required to create a response that your immune system hasn’t figured out how to trigger naturally, which is a difficult task. Scientists believe that the key to such a vaccine is in the antigen (the active ingredient) in vaccines.

Viral coat proteins are generally the easiest antigens or parts of the influenza virus for the immune system to access. But vaccines don’t have to be constrained by normal influenza biology because scientists can design vaccines using methods, strategies or ingredients not available in nature.

The influenza virus contains internal proteins, such as the matrix protein and the nucleoprotein, that don’t mutate frequently. And even the ever-changing hemagglutinin and neuraminidase proteins have parts (called either domains or epitopes, depending on their size) that don’t frequently mutate. But these are normally hidden from the immune system.

These protein parts are all possible targets for a universal vaccine. Couple these novel antigens with advances in vaccine manufacturing and delivery, and the scientific prospects for universal or broadly protective influenza vaccines are bright.

Hurdles on the horizon

But sadly, clever ideas alone don’t bring a vaccine to market. A new kind of vaccine would face a number of barriers before it could ever be administered to the general public. These include regulation, financial incentives for its creation, and policy.

Influenza vaccines are approved by regulatory authorities based on the response the vaccine generates toward the frequently changing portion of hemagglutinin. If a vaccine doesn’t rely on that particular portion of the viral coat, it doesn’t have a clear or inexpensive path to regulatory approval.

Also, a broadly protective vaccine may not need to be administered every year, which would cause a pricing conundrum. A universal vaccine would need to command a much higher price or it wouldn’t be as commercially viable as current flu vaccines, which are administered every year.

But to get to even that point, the vaccine must overcome current policy barriers. Many countries recommend current influenza vaccines for large portions of their populations – as is – with no improvements. This is clearly a disincentive for investment in influenza vaccine innovation.

Clearly, this is one puzzle that cannot be solved with brilliant science alone. If we want to solve a problem that even nature can’t, we’ll need much more than clever science.

We will need smart innovations in regulation as well as market incentives to make universal influenza vaccines a reality. Are we up for the challenge?

Click on the links below for:

  • A report I co-authored on all the aspects of vaccine manufacturing to identify the barriers to a novel influenza vaccine

  • A review describing the current options for cross-protective or universal influenza vaccines

  • A review and commentary on the host-response necessary to obtain universal protection from influenza vaccines

This is the seventh article in our series Facts about Flu. Click on the links below to read other instalments in the series.

Part one: Of influenza, flu, potions and key opinion leaders

Part two: Influenza vaccine for 2013: who, what, why and when?

Part three: H1N1, H5N1, H7N9? What on earth does it all mean

Part four: The Tamiflu saga shows why all research data should be public

Part five: CSL’s flu vaccine leaves a hole in Australia’s pandemic plan

Part six: Should flu shots be mandatory for health-care workers?

Part eight: Is it really the flu? The other viruses making you ill in winter

Part nine: The heart of the matter: how effective is the flu jab really?

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