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Influenza Pandemics and a ‘One-Punch’ Vaccine: An Interview with the IIDR’s Dr. Matthew Miller

In his most recent publication, infectious disease expert Dr. Matthew Miller and colleagues find that being born during influenza pandemics enhance the risk of death during later pandemics. We sit down with Dr. Miller to learn more about the global implications of these findings, what important steps his team at McMaster is taking next, and how the development of a novel universal flu vaccine could ultimately eradicate this risk.

Dr. Matthew Miller, Principal investigator of the Michael G. DeGroote Institute for Infectious Disease Research.

Before we get more into your research, could you explain the difference between a seasonal outbreak and a pandemic?

There is a tremendous diversity of flu viruses in nature. The natural host of influenza is ducks and geese. But over time, the flu adapted to be able to cause infections in a variety of different animals – from chickens and turkeys to sea lions and horses. Pandemics happen when a flu virus that usually comes from animals reassorts – meaning, it mixes its genetic material with another flu virus – allowing it to infect humans.

Because the reassorted virus looks very different than any of the seasonal flu viruses that our immune system has ever seen before, our immune response against it is not protective. The viruses have a huge advantage and spread globally, creating a pandemic. Because the global population eventually develops immunity to the virus, the virus continually mutates so it can continue to evade the immune response. This is what causes seasonal outbreaks.

Your most recent research suggests that people born during flu pandemics have a higher risk of death during later flu pandemics. Can you explain how you were able to find this correlation?

We looked at the birth year of everyone who died during the 2009 pandemic in the USA and Mexico and found a pattern between people who were born in certain birth years and higher than usual risks of death. We compared those people’s risk of dying during a pandemic to their risk of dying during the ten seasonal flu outbreaks that preceded the flu pandemic, which gave us a way to pick out the trends that were specific to the pandemic with a high degree of confidence. We recognized that people who were born in 1957 had an unusual peak in mortality during 2009, and knew that in 1957 there was an H2N2 pandemic called the Asian flu. In conclusion, we were able to see a continual elevation in the risk of dying during future pandemics within populations of people born during pandemic years, despite the creation of vaccines and better health care.

What is different about the immunity of those born during a pandemic, than say, yours and mine?

That is what we are now trying to find out. Because this study was based on epidemiological data, we have not determined the biological basis of the elevated risk. But, there are two main possibilities that we are currently exploring at McMaster. First, flu pandemics tend to be more pathogenic than the seasonal flu. So, it is possible that if you get infected with the pandemic virus at a young age, this causes some sort of damage to the lungs that makes you more susceptible to severe respiratory infections later in life. A second possibility is that encountering this first flu pandemic early in life generates an abnormal immune response when infected with a pandemic later, in such that instead of protecting you, your immune system actually causes you to have worse symptoms. This is something that we call a dysregulated immune response.

Why is this research important?

There are two primary implications that arise from this work. The first implication affects government and policymakers. We all know that flu pandemics happen regularly, and, unfortunately, until there is a universal vaccine, there is nothing we can do to stop them. When pandemics occur, policymakers have plans in place about who gets treatments, drugs, and new vaccines first; typically, those who are at a higher risk of dying from flu. But, what our study suggests is that the age of people who seem to be at high risk are an age group that we would normally consider to be low risk – an age group that is generally young and healthy. Now that we know that people born in the years of pandemics have this unusually high risk, we could make sure that they are amongst the first to receive medical provisions in the event that another pandemic happens. This implication can take place almost immediately.

The second implication would arise from understanding the biological reason of why this is happening. Is the virus causing this population’s lungs to be compromised from an early age? Or is this an immunological phenomenon? If we can figure out what is happening biologically, then when we can aim towards designing more specific drugs and treatments that better protect this higher risk group.

If a universal vaccine were to be developed and made available to the public, would it offer better protection to this high-risk population than seasonal flu vaccinations?

Yes. Because the flu continues to mutate, we have to remake seasonal vaccines every year based on which strain we think will circulate. Since we are not very good at guessing how the virus will mutate, we sometimes incorporate a strain that isn’t actually circulating that season. That is one problem – but I would argue that this is the lesser of the two main problems with the seasonal vaccine.

The bigger problem is that seasonal vaccines do nothing to protect us against pandemics – and it is pandemics that we are really scared of when it comes to the potential mortality tolls and economic implications. An unfortunate reality is that when pandemics happen, they happen so quickly that we can’t reactively make vaccines or therapeutics fast enough to give people adequate protection. We know this because we tried in 2009 with the Swine flu virus – less than 10 years ago. Once people recognized that the Swine flu was going to cause a pandemic, we tried to make a brand new vaccine for that virus – but by the time the vaccine was made and shipped to hospitals and pharmacies, the pandemic was over. So, we really know that we can’t move fast enough to make a new vaccine in the event of the pandemic – and there haven’t been any huge technological advancements since 2009 to lead us to believe that we could do any better now. We were really lucky in 2009 because that virus wasn’t a particularly strong virus in terms of the severity of illness that it caused, but that was pure luck. The next one could be 100 times worse, and we have no way of really knowing in advance. The development of a universal vaccine is really the only viable option that could proactively protect people from pandemics.

So, a universal vaccination would be able to protect against future pandemics, whereas a seasonal flu shot possibly could not. 

Exactly.

Dr. Miller is an Assistant Professor in the Department of Biochemistry and Biomedical Sciences at McMaster University, and a member of the Michael G. DeGroote Institute for Infectious Disease Research and the McMaster Immunology Research Centre. Dr. Miller is currently working with scientists at the Icahn School of Medicine at Mount Sinai, New York on the novel development of a “one-punch” universal flu vaccine. Find out more about his past and current research at www.themillerlaboratory.com.

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