Protecting, Anti-'flu Viruses

13 December 2009

Interview with

Nigel Dimmock, Warwick University

Chris -   We've heard about vaccines offering one way to combat flu.  We've also got antiviral drugs like Tamiflu to fall back on.  But, as we've heard, the virus can mutate.  And some of those forms can become drug resistant.  So is there anything else we can do?  Influenza Virus

Well, Dr. Nigel Dimmock is a researcher at Warwick University and he's looking at a different antiviral approach.  He's infecting people with what are called protecting viruses.  And he's with us now.  Nigel, what is a protecting virus?

Nigel -   Well, Chris, a protecting virus is something which is absolutely new in terms of treating virus infections.  The lovely thing about protecting viruses is that they are actually made by the virus itself.  It's a big mutant of the virus.  Now, the thing is that all viruses make them as I say.  And they are antiviral. 

So what we get is a virus, a perfectly normal-looking virus, but it has a genome from which a large chunk has been excised by some accident of replication.  Now, what happens is that when this gets into a cell alongside an infectious virus, the infectious virus multiplies itself.  But it also multiplies the defective form which we call the protecting virus.  And because of the dynamics, there's much more of the protecting virus made than of the infectious stuff.  So what happens is that the protecting virus swamps out the infectious virus.  The virus is aborted and you get better.  And it essentially buys time for the immune system to mop up the infection.

Chris -   So, in a nutshell, you have a flu virus replicating.  Normally, it's got to copy all of its genetic material making new progeny viruses. These come out and infect other cells and when they've infected lots of cells, that makes you feel sick and you've also got the opportunity to infect other people.  With the protecting virus, it's a modified form of 'flu which can arise by chance but which has defective genetic material and is easier for it to grow than the follow on normal flu.  Therefore it gets in the way, puts a spanner in the works, so you make less flu.  You are less infectious and you are less infected and therefore, you don't feel as bad.

Nigel -   That's absolutely right.  And there are various very nice things about this;  one is that you could be treated with this protecting virus by, for instance, a nasal spray.  Now remember, it is flu virus.  So it knows which cells to go to.  It goes to exactly the same cells as the regular flu goes to but it's not infectious.  So, if that happens, then the protecting virus genome will sit in this cell.  And it will slowly decay, but a single dose will provide you with protection for certainly a number of days and perhaps weeks.

Chris -   Presumably also, Nigel, because of the way flu works with all of its genes as little miniature chromosomes, these so-called ribonucleic proteins, it doesn't actually matter what strain of flu you'll get infected with.  This interfering or protecting virus will basically protect you against virtually any type of flu.

Nigel -   Yes.  This is one of the other very good points about protecting virus, is that unlike the vaccine which is be absolutely specific for the strain against which it was made, this protecting virus will protect you against any strain of flu A.  You don't even need to know what you're infected with as long as it's flu A; the protecting virus will protect you willy-nilly.

Chris -   And presumably, the other benefits is that you will make some antibody against a flu anyway which will help.  But doesn't that mean then that if someone already has antibodies - because they've already had a dose of the flu in the past - they might not get very well infected with your protecting virus?  And therefore they wouldn't get any benefit from it because they're already immune.

Nigel -   Yes, this is a technical point which means that you have to choose a virus to deliver the protecting genome which people haven't had.  So what we're using is actually a strain which was isolated in 1934, one of the very first flu strains to be isolated.  And it's the same one that is used as the work horse as we've heard earlier in the production of vaccines.  So there are not many people who were around in 1934 around now.  And if they were, their antibodies are rather decayed.  So it's a perfect delivery vehicle.

Chris -   That's all very well.  But then once you've used it once, those people presumably can't derive benefit again because they will then be immune.  So you'll have to change the virus, won't you?

Nigel -   No, that's not right.  No.  We give a very low dose.  It's a far lower dose than you'll get with the vaccine.  And this is another key point about protecting virus because it does work at a very low level.  So you don't need to produce as much as you would with the vaccine.  And because it's at this low level, it's not stimulating immunity. 

Now, when you get infected, the virus that is produced is the infecting virus.  Not the virus that delivered the protecting genome.  So you're not producing more of the protecting virus but you're producing simply more of the incoming infectious virus.  So the immunity will be against the infectious virus, not the protecting virus.

Chris -   Which sounds encouraging.  And just to finish off, can you tell us when we might be able to see this actually being used because obviously, this is an experimental tool of the moment.  To my knowledge, this has not gone into patients, has it?

Nigel -   No, that's absolutely right.  We've done a huge amount of lab work. It works very well under experimental situations.  But the thing now is to get it into human clinical trials.  As you are aware this is a hugely costly business and what we're engaged with now, with the university, is in raising money to carry out these clinical trials.  And then we shall really know whether protecting virus is a real prospect for human medicine.

Chris -   So if anyone wants to write you a cheque, just write your cheques out to Nigel Dimmock in Warwick University...  I'm just joking, Nigel.  But thank you very much for joining us.  It's been great having you on the show.

Nigel -   Absolutely.

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