Virus-Like Particles May Mean Speedier Flu Vaccines

We've been talking a lot lately about flu vaccines. Now an anonymous reader sends us to a Technology Review piece on two human trials involving so-called virus-like particle vaccines, which promise to be much faster to churn out than traditional vaccines. (Here's a single-page version but without the useful illustration.) VLP vaccines use a protein shell, grown in either plant or insect cells, that look just like real viruses to the body's immune system but that contain no influenza RNA genetic material. A company called Medicago grows its VLPs in transgenic tobacco plants, while another called Novavax uses "immortalized" cells taken from caterpillars. Providing they pass safety muster, both techniques should be able to produce an influenza vaccine more quickly than current methods, using just the DNA of the virus.

Comments

Flu !DNA

[Red Flayer]

Providing they pass safety muster, both techniques should be able to produce an influenza vaccine more quickly than current methods, using just the DNA of the virus.

Sorry to nitpick, but influenza is an RNA virus, not a DNA virus.

I have no clue if this makes a difference in how quickly a vaccine could be made using this technique, but I just needed to get the "Friday Pedantry" out of the way.

Re:Flu !DNA

[sumthinboutjesus]

Good catch on the RNA vs. DNA. However, this would not effect how quickly a vaccine could be made with this technique nor its efficacy, as it is just training the plasma cells to recognize a folded conformation and produce antibodies to bind that 3d conformation, allowing the immune system to clear it after the virus is bound (opsonized).

Re:Flu !DNA

[Anonymous Coward]

Although influenza is an RNA virus, researchers are probably generating a cDNA library of the flu structural proteins and using these DNA templates to transfect their cellular expression systems, resulting in the production of the virus-like particles. This may be the source of confusion in the summary above.

Re:Flu !DNA

[RDW]

For standard flu vaccines, the speed of production depends on quite a few steps, some of which can be carried out in parallel (e.g. clinical trials can start before all batches are made), while others need to be done in series (e.g. bulk production can't start until growth conditions are optimised):

http://www.who.int/csr/disease/swineflu/notes/h1n1_vaccine_20090806/en/index.html

One advantage of the VLP approach is that you can produce the relevant proteins in standard biotech 'factory' organisms, which avoids the laborious and time-consuming process of culturing live virus in hens' eggs. Reverse-transcribing the viral RNA is no big deal - this happens in the initial phase of characterising a new virus in any case (for sequencing etc.) long before vaccine production begins.

Re:Typical big media...

[Red Flayer]

You guys are running around producing Immortal caterpillars and noone let me know? Bastards!

Well, I, for one, welcome...

Sorry. Just couldn't do it.

Here are the problems with immortal caterpillars... If they behead eachother, do they gain in strength? Do they ever turn into moths/butterflies, or do they maintain immortality by staying in caterpillar form?

I mean seriously, you're a caterpillar, and you're immortal. Do you forsake immortality by spinning a chrysalis just so so you can have sex, live for a few weeks, and then die?

These are the questions that keep me up at night (and coincidentally, prevent me from having sex while NOT providing any form of immortality).

Bonk bonk on the head

[Tablizer]

I explained traditional vaccines like this to my kids: "What they do is get some of bad viruses, we'll call them little monsters. So they clone these monsters (kids learn what cloning is from cartoons) and then bonk them in the head to make them all dizzy. Then they send these dizzy monsters into the village, which is your body. The villagers see the monsters and beat the Cheerios out of them, and then kick them out of the city. They also learn to recognize the monsters. So when the real monsters come, the ones that are not dizzy, the villagers know how to recognize them because they look just like the dizzy ones. That's how they know to find the monsters and kick them out."

Kid: "But daddy, why don't they just put up a Wanted poster?"

Me: "Uh, go ask your mom."
     

Re:Bonk bonk on the head

[CheeseTroll]

Are you a Nintendo game designer, by any chance?

Re:Bonk bonk on the head

[geekoid]

Funnny, but what the kid asks uis actually closer to how a vaccine works.

A dizzy monster might recover and go rampaging through the village. The flu vaccine is not a live virrus and as such it is like putting a wanted poster up.

Re:Bonk bonk on the head

[baKanale]

Most flu vaccines are inactivated. On the other hand, "live attenuated influenza vaccine" is reduced in virulence but still "alive", and "may cause an infection with complications in people with weakened immune systems or other underlying medical conditions."

http://en.wikipedia.org/wiki/Live_attenuated_influenza_vaccine#Risks

Re:Bonk bonk on the head

[mikael]

The nasal spray version of the vaccine does contain live virus, but "attenuated" so that it can only reproduce in the lining of the nose.

Re:Bonk bonk on the head

[Schickeneder]

They do put up wanted posters. They're known as major histocompatibility complexes!

http://en.wikipedia.org/wiki/Major_histocompatibility_complex

Re:A new method of vaccine delivery?

[Tablizer]

So tomorrow's vaccines can be administered by cigarette?

The tobacco industry must be just jizzing about this.

WARNING: The Surgeon General has determined that NOT smoking this pack of Joe Camel the Flu Slayer(TM) may be hazardous to your health.

Re:I'm surprisde no one's done this before

[ColdWetDog]

since antibodies react to proteins or other structures and not the RNA/DNA. Maybe profits on vaccines aren't really there?

Or, alternatively, they've been trying for a long time without success. FTFA:

VLPs have been an around-the-corner promise for over 20 years. But they've now reached a stage at which even disinterested observers believe, as Columbia University virologist Vincent Racaniello put it, that VLP vaccines "really seem to be coming into their own."

But don't roll up your sleeve just yet. Sounds a lot like holographic storage, Duke Nukem Forever, better batteries, flying cars, jet packs, sensible women.

Re:I wonder...

[crmarvin42]

This solution would probably require much higher doses than current vaccines do, but it would probably be safer and faster.

The flu at least is an RNA virus, but the function of the genetic material is for the replication of the virus after it has infected a cell. When it is not actively infecting a cell the DNA/RNA is completely dormant within the viral coat, thus the debate over whether viruses are alive or not. There is no metabolic activity in the absense of a host cell to infect.

The shell or viral coat is primarily what the immune system recognizes when fighting a viral infection. That is why killed vaccines work. They don't work as well as modified live vaccines (generally) because you don't get the first couple of generations of viral replication (at a slower rate than the wildtype virus) that trigger a much stronger immune response. Viral RNA can also trigger immune response, but the RNA needs to be processed by an antigen presenting cell such as an infected cell or a phagocyte.

It actually works the same way with certain bacteria. Researchers will frequently inject LPS (lipopolysaccharide) into animals to simulate a bacterial infection, because bacteria have LPS on their surfaces and their are immune systems designed to recognize this ubiquitious bacterial component.

I'm not sure about separate shells, but I do know that many (all?) viruses have several different proteins involved in making the shell, and that changes in which proteins are present will change the antigenic profile of the virus.

Re:no flu vaccines for me thanks

[rrohbeck]

Serious side effects from vaccination are on the order of one in a million or less, serious disease from the flu is on the order of one in thousand or more.

They're not the only ones...

[guzziguy]

Antigen Express is working on a synthetic flu vaccine that doesn't use tobacco or caterpillars:

http://www.masshightech.com/blog/2009/09/25/antigen-express-synthetic-h1n1-flu-vaccine-in-the-works/

production in insect cells has advantages

[airuck]

One great advantage in using insect cell lines is that they do not require serum to grow, which is both costly and open to the risk of transmitting zoonotic pathogens. Insect cells can also be more robust than mammalian cells in large scale fermentation conditions.

Re:no flu vaccines for me thanks

[ChromeAeonium]

I could have modded you down, but since there is no -1 Wrong moderation, I decided to correct you instead. When you use a vaccine, you ARE relying on your immune system. All vaccines do is help create an immune response in a manner usually safer than the disease. I say usually because vaccines aren't supposed to eliminate all the risk. That's impossible; all reward has risk. Would you rather have, for example, a 1/50,000 chance of getting hurt by the flu, or a 1/1,000,000 chance of getting hurt by the vaccine. Those aren't actual statistics, but you get the idea. It is true that people are hurt by vaccines, and yes, they sometimes die from the vaccine, but the point is that they're safer than not getting vaccinated. I don't know why there has to be this false dichotomy that because a vaccine is not absolutely perfect that it is dangerous. I mean, it would be like claiming that you shouldn't wear a seat belt or use airbags because people have been hurt by those things. They save many, many more than they harm. It is not about eliminating danger, it is about mitigating the danger to lower levels. It is just asinine and illogical to say that because vaccines aren't fairy dust panaceas you shouldn't get one. I hope people realize that the vast, vast majority of this anti-vaccine nonsense has its cultural roots in anti-scientific fear-mongers (lookin' at you, Wakefield), not actual fact.

Re:I wonder...

[nietsch]

I am a Biologist, please allow me to answer:
Yes the DNA or RNA has a function: to make more virus. immune reactions work on anything the immune system recognises, and because the immune system is built with protein, it is mostly protein it recognises. Naked DNA or RNA in the bloodstream is quickly mopped up, so you do not need specific immunity.

Vaccination does not trigger an immediate response if you have never seen the antigen before (and if you have, the vaccination is needless and poses a risk). It takes some time to mount an immune response, about as long as 'the flu' lasts. once this response is established, your immune system 'remembers' it. A next exposure to the antigen will see a much quicker response to the antigen, and the second exposure will also reinforce your long term immunity. Read up on immunity if you still don't trust it, this is basically just how it works.

The flu virus evolves a new shell almost every season, exactly because the immune system reacts on its outer envelope. 'They' have no system to switch between different env genes, as you'd need a lot of overhead for that. Having a lot of mutations between each generation and letting basic evolution take its course works much more efficiently.