Our Fight Against Flu

UGA's Ted Ross and colleagues pursue a scientific Holy Grail


The flu shot is an annual ritual for fighting a deadly disease. But six out of 10 Americans never get it. Some don't like needles; most just don't get around to it.

What if we didn't need the shot every year? What if a single vaccine would protect us from all forms of flu — for the rest of our lives?

GRA Eminent Scholar Ted Ross and colleagues at the University of Georgia are in hot pursuit of a universal flu vaccine, considered a Holy  Grail of science and medicine. They're using a technology called COBRA — and it's an approach that's capturing attention.

After filming the video, Ross — who heads UGA’s Center for Vaccines and Immunology — was kind enough to answer a few questions about the flu and vaccine research in general.
 

You once said, “Many of the easy vaccines have been developed.” What makes it so much harder to develop vaccines for diseases like influenza and malaria vs. polio or measles?

For one, when humans are the only host, we have only one species to target. For example, there’s only one version of mumps – human mumps. So if you’ve made a vaccine against mumps, you’ve made it against all mumps. Same with smallpox and measles viruses. But something like HIV has billions of versions of its genome.

 

You probably get asked this often: When we will have a universal flu vaccine?

The reason it’s hard to say is you’ve got to address not one thing, but three things. First, you have to design a vaccine against all the various strains of flu that circulate. Second is how long that immune response can last. Finally, you’ve got to be sure the body’s immunity works equally well for people of all ages.

 

And your group is working on that first thing – the different strains of influenza virus?

That’s right. We’re working to generate a vaccine using a protein from the influenza virus called hemagglutinin. This ‘H-molecule’ is the target of most of the antibodies that neutralize the virus. Instead of working with single wild-type strains, we’re engineering in the lab – and putting together, like a mosaic – pieces of all the other different strains out there into one molecule, a synthetic molecule.

 

What makes a normal outbreak of the flu become a worldwide threat – a pandemic?

Influenza’s reservoir is wild birds, mainly geese and ducks. Most of the strains don’t affect people. But every once in a while, you get a bird strain that’s able to infect us and can be transmitted. When that happens, it’s when we have a pandemic. We had one in 2009, which turned out to be milder than most. And of course, we had famous pandemics in 1918, 1957 and 1968. It’s inevitable that this is going to happen. Within the next 30 or 40 or 50 years, there will be some change in influenza, and everyone will be susceptible again. And as long as we have geese and ducks on this planet, we’re never getting rid of influenza.

 

We read where you’re testing a vaccine to fight many types of H5N1 influenza. What’s that about?

The H5N1 flu vaccine is our oldest, so it’s the farthest along. Avian H5N1 flu was the hot thing in the mid-2000s. It hasn’t become transmissible among humans – some people contracted it after directly interacting with infected birds. But it looked like it had a very high mortality – 70 percent. For most flu, the mortality rate for healthy adults is around 1 percent. So a lot of people worried that H5N1 and other pandemic strains of influenza could become transmissible from person to person. If that happened, it could cause something like the 1918 pandemic.

 

How does your work on that vaccine relate to a universal flu vaccine?

We asked, how can we make a new vaccine to these subtypes [of H5N1] that we don’t even know exist? We don’t have any information about them. We had to design for something that’s going to happen in the future. So we knew we had try to make a vaccine for all of the H5N1 subtypes. In sort of a backwards way, we walked ourselves into, well, if we can do this for bird flu, why can’t we do this for regular, seasonal human flu? Can we make a vaccine that reacts against every flu strain?

 

What is a typical day like? How do you set priorities?

We work in groups, with team leaders. In my lab, we have four different teams. We meet once a week. People present data. We outline what will happen in the next week or two. We set strategies and priorities. But they all work together – you can’t do this without a team.

 

When we get to a day when there are so many more vaccines – how will all of those get administered to someone?

Some can be combined together, as we do now with childhood vaccines. The more you can put into one shot, the better. A lot of parents now get worried about having too many vaccines at once, and they want to spread them out. In reality, there’s no basis for that. You can give them all at once, and it’s not going to make it a worse response or anything. Actually, spacing them out sometimes means you’re not giving them at the right intervals, and that leaves children vulnerable. 

 

What would most benefit your research – what would help advance or accelerate it?

There are a lot of good ideas that die after pre-clinical trials. Getting to the clinic is difficult, especially from the academic point of view. You’ve got to have a partner that can manufacture and market your licensed vaccine. We’re not equipped here to take something all the way to Phase III clinical trials.

There’s this gap between when you finish the proof of concept and when you begin testing it in the clinic. Unless you have an organization inside your university that can help you do the license, do the toxicity screening, file the FDA application, write your Investigational New Drug application – all of that you usually have to partner with a company that has the resources to move it forward.

 

So how much of a priority is flu?

It’s very hot. First of all, flu is never going to go away. And every season, you get a nice publicity boost. Every season it comes around – it’s always in the news.