Fluvirus-antigentic

The above image shows the different features of an influenza virus, including the surface proteins hemagglutinin (HA) and neuraminidase (NA).

Geese are migrating south, and this year’s flu vaccine is at pharmacies. Have you ever wondered why we need a new flu vaccine every year? Or why there isn’t a single-shot, life-long flu vaccine?

Unlike polio and most other viruses, influenza isn’t one uniform virus. Instead, influenza is a swarm of closely related, yet distinct viruses that change their genetic material every year as they move through ducks and pigs before infecting humans. For this reason, scientists across the globe closely monitor influenza virus infections. This information helps researchers make an educated guess about which flu strains are likely to infect people, and use those strains to make the annual flu vaccine.

Some years this process is accurate and vaccine protection is high, but in other years, unanticipated flu strains arise and the vaccine does not fully protect us. This uncertainty is the driving force behind the push to develop a universal flu vaccine that would protect against all strains of influenza, regardless of what specific virus arises in a given year.

A one-shot, universal flu vaccine would have an immediate and powerful effect. The Centers for Disease Control and Prevention estimates influenza results in more than 400,000 hospitalizations and 42,000 deaths every year in the U.S. Sadly, these deaths are often among the most vulnerable in our population, namely the elderly, children and those with pre-existing medical conditions. These numbers make influenza a clear and present danger to our society.

I know firsthand how serious influenza infections can be. In the summer of 2014, my then 5-year-old son contracted swine flu and wound up in the emergency room. Although he recovered, this experience personally motivated me to join the effort to develop a better influenza vaccine. Thanks to a Grand Challenges grant from the Bill & Melinda Gates Foundation and the Flu Lab, I and my OHSU colleagues have the opportunity to develop and test a radical new approach toward a universal influenza vaccine.

Every successful vaccine developed to date functions by directing your immune system to remember and target viruses with antibodies, small proteins that stick to the outside of viruses and prevent them from attaching to their target cell. If a virus cannot attach to its target cell, then it cannot infect that cell. While this process works well for viruses that don’t change their outer appearance (like poliovirus), focusing the immune system’s memory on the outside of the virus turns out to be an Achilles’ heel for influenza vaccines. This is because the outside of the influenza virus is the part of the virus that changes the most. The influenza virus is constantly evolving its outside appearance, making our current vaccines continually chase the virus as it changes over time. The new approach we are proposing will instead teach T-cells, the assassins of our immune system that kill infected cells, to target the guts of the virus, which are fixed and cannot change their appearance. I imagine this new approach as training a bull (our immune system) to ignore the waving red cape (the outside of the virus) that the matador is waving, and instead charge directly at the matador. While this might sound unrealistic, the approach is rooted in more than 10 years of research by our collaborative research team’s greater ability to develop a vaccine platform based on cytomegalovirus (CMV), a common, mostly harmless herpes virus with which most people are already infected. OHSU’s CMV-based vaccine platform has already demonstrated promising pre-clinical efficacy against HIV and TB. The CMV-based HIV vaccine, for example, is headed into human clinical trials that will be managed by San Francisco-based Vir Biotechnology, which licensed the technology from OHSU.

So the million-dollar question is, will this new approach work? We’ll test our CMV-based flu vaccine’s effectiveness against one of the worst flu strains ever: the 1918 pandemic flu strain, which killed 50 million people worldwide. Within two years, we’ll know if our CMV-based flu vaccine can fight off the 1918 flu strain. If it can beat that, it can probably beat any flu strain. And while we don’t know for sure if it’ll work, I’m proud to be part of this effort to help society once and for all beat the flu.

— Editor: 541-633-2166, gobrien@bendbulletin.com

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