Scientists Take Step Toward Universal Flu Vaccine

Flu shots keep many people healthy, but can't fight all viral strains. Now scientists may be a step closer to creating a vaccine that fights all strains. Molecular biologist Ian Wilson explains how researchers are trying to trigger the body to fight more kinds of viruses.

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IRA FLATOW, host:

For the rest of the hour - a look at efforts to develop a new universal - a universal flu vaccine. How many - you know, how many of you've been through this? You do what your doctor tells you. You get your flu shot. A few weeks or a few months into the flu season, you get sick with the flu anyhow, right? It's happened to all of us, because the way the flu vaccines are made now, they only protect against a couple of strains of the virus. And each season, flu specialists - they make an educated guess at which strains are most likely to show up, and sometimes - they sometimes, they get it wrong, and a strain that no one saw coming makes the rounds, leaving a lot of aches and pains in its wake.

Well, wouldn't it be great if there was a vaccine that could fight any flu strain, any and all - like a universal vaccine? Well, researchers are trying to develop this universal vaccine by tapping into unused flu-fighting resources in the human body. And it turns out that we may already have the antibodies to fight against more kinds of flu. The trick is, how do you activate them? Here to talk more about it is Ian Wilson. He's a professor in the department of molecular biology at the Scripps Research Institute and at The Skaggs Institute for Chemical Biology in San Diego. Thanks for talking with us today. Welcome to Science Friday.

Dr. IAN WILSON (Professor, Molecular Biology, Scripps Research Institute; The Skaggs Institute for Chemical Biology): Thank you very much.

FLATOW: So, you have found an Achilles heel, so to speak, of all flu viruses possibly?

Dr. WILSON: Perhaps not all flu viruses, but a substantial number of different types of different strains and different subtypes. We have an antibody, which we've been working on with a company in Holland called Crucell. And they've actually managed to pull this antibody out. And we've been looking to see where it binds on influenza virus. And we actually found that it binds to a very conserved region on the virus, which is present in all different strains and subtypes of flu viruses. And so, this gives a possibility then of generating such antibodies in our body against that particular site.

FLATOW: Well, if this site has been around, has it been known about for a while?

Dr. WILSON: Not really. There have been some suggestions that you might be able to get antibodies in that region. But the reason that we don't produce those antibodies is that you tend to bind - our immune system tends to make antibodies against the parts which are most exposed. And if you think of the hemoglutinin then as if a spike that extends from the virus, then we have a head and we have a stalk region.

FLATOW: You have like a little lollipop sticking out?

Dr. WILSON: That sort of thing. You make - generally make antibodies against the tops of the lollipop, not against the regions which are further down on the stick.

FLATOW: So, by looking further down on the stick, you have found a common region that really doesn't change much?

Dr. WILSON: It certainly doesn't change much from strain to strain. There are things like sugar molecules which can cover parts of these regions up. And that's why this antibody doesn't bind to all of the different subtypes of flu, but it binds to a large number of them.

FLATOW: And you say that there are drug companies testing this now?

Dr. WILSON: Currently, these antibodies have been produced, obviously somewhat in vitro, and the question is, can we try to see if we can now use this information in some strategy to actually elicit those antibodies in our bodies? That's quite clearly going to be a very difficult challenge, but we now know sort of a blueprint as to what region to go after.

FLATOW: So, what you're saying is that we have to find a way to get our bodies to react defensively to find that antibody site when we're attack by that virus?

Dr. WILSON: That's correct. And so, that's going to take quite a lot of work and doing some sort of vaccine design-type studies to try to see if we an elicit those type of - that type of response from a vaccine.

FLATOW: There's also a very similar bit of work that's going on at Harvard, right? They're looking for a universal flu vaccine, too?

Dr. WILSON: That is correct. I think now that there's really been three independent studies - one from our present here at Scripps, that - who looked at some antibodies from Turkish survivors last year, and the study that you're talking about from Harvard - from Burnham and from the CDC. And what's really exciting is that all three studies appear to have pulled out the same family of antibodies that bind to the same region on the virus.

FLATOW: Let me go to the phones - Holly in Long Island. Hi. Welcome to Science Friday.

HOLLY (Caller): Yes. Good day to you gentleman. I would like to know that under an electron microscope, can the particular virus that you think could be a uniform virus antibody for viruses in general - would it take a certain shape or form that you could recognize immediately?

Dr. WILSON: As far as the flu virus itself is concerned?

HOLLY: Yes, sir.

Dr. WILSON: Flu viruses tend to be - have - adopt really different shapes, but by and large you can actually recognize that influenza virus from the sort of spikes that stick out from the surface of the virus.

HOLLY: Thank you.

FLATOW: Thank you, Holly. So, there - describe what the virus looks like. What are these spikes and why are there so many of them?

Dr. WILSON: Basically, the virus - it can be round. It can be long. It can be sort of tubular. It can adopt various shapes. These spikes stick out of the virus. They're sort of like long protrusions. They're sort of like little rods sticking out or as you say, like a lollipop. There's probably about 100 or more of these on each virus. And it needs these spikes, because the virus has to bind to our cells, and it needs to get inside our cells. So, it uses the spikes to be able to bind to the surface of our cells through receptors, and then, once it gets into the cells, it's got to be able to get its own genetic material inside our cells. So, it really uses that to actually fuse the surface of the virus - it's own viral membrane - with a membrane in our host cell and - to - in order to get the genetic material inside the cell.

FLATOW: Now, what would a vaccine do to prevent that penetration of the virus into the cell?

Dr. WILSON: So, the vaccine really - so you can try to stop it - stop the virus entering the cells in two ways: You can stop it binding to the receptors or you can stop it fusing during the membrane fusion event. Most of the antibodies that we have bind to the top of the hemoglutinin spikes. And they are really around the receptor binding site, thereby preventing binding to the cells. This particular sets - these particular sets of antibodies appear to not prevent that process but to prevent the fusion process by binding and preventing three-dimensional rearrangements that are required for these fusion events.

FLATOW: Talking about flu vaccine development this hour on Science Friday from NPR News. I'm Ira Flatow talking with Ian Wilson, professor in the department of molecular biology at Scripps Research Institute. So, let me see - well, a couple of more questions here. Let's see if we can go to the phones - 1-800-989-8255. David in Phoenix. Hi, David.

DAVID (Caller): Hi. How are you?

FLATOW: Hi there.

DAVID: Professor Wilson, I have a question that's sort of on the other end of the vaccine question. I'm excited about the new flu vaccine but for a different reason. I'm allergic to eggs and have always been told by, you know, people giving the vaccines that I cannot get it for - I assume for the reason that it's developed in egg albumin or something like that. And I'm wondering, is this new way of attacking or of developing this vaccine and attacking the flu virus going to be done in such a way that me and in fact my sons, who also have inherited my allergy, can actually get the vaccine?

Dr. WILSON: Yes, that's a very good question. I'm not sure I can really answer that. You're absolutely right that most of the vaccines are actually produced in eggs. We don't have any vaccine. We just have some possible ideas of how one might actually generate such a vaccine. That's going to take a number of years, and it's not clear how that will be developed. So, I wish I could actually answer your question. But I'm afraid at the moment, we're still probably a number of years away from actually having that vaccine.

FLATOW: Let's go to Michael in Portland. Hi, Michael.

MICHAEL (Caller): Hi. How are you, Neal - or…

FLATOW: It's Ira today.

MICHAEL: Ira.

FLATOW: It's OK. We sound alike. Go ahead.

MICHAEL: I was wondering if the development of a flu vaccine from multiple strains of the flu would lead to an increase in drug resistance from all flu strains?

FLATOW: Yeah. How do you know you're not going to make a supervirus?

Dr. WILSON: That's always a possibility, that you could actually get resistance against the particular vaccine. However, there are certainly lots of sites on the hemoglutinin and on these spikes that you can actually bind antibodies to. So, we're not eliminating the possibility of binding to these areas. So, there should only be one area that you'd be focusing in on. And so, I think this - you could certainly get resistance from this. There's always the possibility of resistance from any vaccine, but this would only be for a small area on the virus that would not be for the rest of the virus which is currently available for antibody binding and the present vaccines.

FLATOW: Give me - I got a minute left. Give me a quick lesson in microbiology. How do things bind to each other on these surfaces?

Dr. WILSON: How did the viruses bind?

FLATOW: Yeah. What - is it a mechanical process that goes on? What is going on there?

Dr. WILSON: No, it's a simple - it's actually a sort of a chemical recognition process. Basically, the virus has sort of a little shallow pocket on the surface, and it can bind to sugar residues on the surface of our cells. It actually binds to a particular sequence of sugar residues, which are phthalic acid linked to a galactose linked to another sugar residue. And so, pretty much, it sort of latches on to that sugar, grabs on to it, and because there's a lot of spikes on the surface of the virus, it can bind very tightly through sort of multivalent interactions.

FLATOW: OK. Well, I think that's the first time we've ever had that explained that way. I want to thank you very much for taking time to explain that to us, Dr. Wilson.

Dr. WILSON: You're very welcome. Thank you very much for your time.

FLATOW: And good luck to you.

Dr. WILSON: Thank you.

FLATOW: Ian Wilson, a professor in the department of molecular biology at the Scripps Research Institute and at The Skaggs Institute for Chemical Biology in San Diego. That's about all the time we have for this week. Greg Smith composed our theme music. We had help today from NPR librarian Kee Malesky.

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Scientists Close To Universal Vaccine For Flu

Patient receiving an injection.
iStockphoto.com

American scientists have taken several key steps toward developing a near-universal flu vaccine. If further research works out, the vaccine could fight many types of conventional flu, as well as avian influenza, and even the virus that caused the 1918 flu epidemic that killed 50 million people.

Conventional flu strains mutate over time. And every year, well before flu season, scientists have to predict whether new strains will be coming through. Manufacturers base their vaccines on that prediction, which hasn't always been correct. One of the holy grails of immunology is finding some aspect of a virus that doesn't change from strain to strain, so the exact strain is no longer important.

One Key To Fit All Locks

And now, a group of researchers may have done just that. Researchers from Dana-Farber Cancer Institute, Harvard University, the Centers for Disease Control and Prevention, and the Burnham Institute for Medical Research have identified a man-made antibody that recognizes a component of many conventional flu viruses, the 1918 virus and bird flu viruses. The antibody not only recognizes all these virus strains, it neutralizes them by interfering with the virus' ability to infect cells.

One of the discoverers, Dr. Wayne Marasco of Dana-Farber Cancer Institute, says this so-called neutralizing antibody has two potential practical applications. "It lends itself to a therapy that can be used to prevent and treat a broad range of avian and seasonal influenzas," he says. That is, it may be possible to just inject the antibody into people who've just been infected by the bird flu virus or a conventional flu virus.

Added Benefit

The second potential application is using the protein the antibody attacks as a vaccine. That protein sits in a pocket just beneath the virus' ever-changing coat. Used as a vaccine, it would train the body to recognize and attack flu viruses.

"I think this is a very important conceptual advance," says Anthony Fauci. He heads the National Institute of Allergy and Infectious Diseases, an organization that partly funded the work. "Now we need to translate it into practicality."

The team of researchers who identified the antibody is already working on animal models to determine how the new information can be used. The research is described in an advance online edition of Nature Structural and Molecular Biology.

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