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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.
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.
"Trolls they were, but filled with the evil will of their master: a fell race..." -- J.R.R. Tolkien on Olog-hai
As a future healthcare provider, I certainly hope that vaccines like these will be proven safe and effective. Their promise lies in the ability for the production of vaccines against the dominant strains in a much quicker manner. If we had these methods approved for the current flu season, the industry wouldn't have been caught with its pants down when the H1N1 strain became dominant and hit much more quickly than planned. The vaccines were targeted to be ready for about a month or two from now, and the virus has hit much harder much sooner than anticipated. If these techniques take off, hopefully this situation can be mostly avoided in the future.
A company called Medicago grows its VLPs in transgenic tobacco plants...
So tomorrow's vaccines can be administered by cigarette?
since antibodies react to proteins or other structures and not the RNA/DNA. Maybe profits on vaccines aren't really there?
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).
"Trolls they were, but filled with the evil will of their master: a fell race..." -- J.R.R. Tolkien on Olog-hai
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."
Table-ized A.I.
Is this how the Umbrella corp got their start in creating a Zombie virus?
Hopefully these researchers have created a decent underground lab, with flooded rooms, insane computers, dogs ready to be zombiefied, lots of corridors, exotic weapons with ammo dropped in numerous random places, and other useful stuff. If I was building a virus lab, I'd definately need to have all this available in case someone needs to sneak in and blow it up.
Who would win this election: Andrew Weiner vs Andrew Weiner's weiner.
The outer shell is the primary approach the body uses to recognize viruses. As far as I know, it's the only way other than filtering out small particles in general, which can be tricky and metabolically expensive because legitimate stuff can also be that size.
Mutating the outer shell is one of the key ways viruses use to survive and prosper. That's the main reason everybody gets sick during the flu season. Aids is especially tricky because it has a slimy or fluffy outer coat that is hard to analyze by the body's defenses.
Table-ized A.I.
C'mon folks, did nobody watch I Am Legend?
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.
Bureaucracy expands to meet the needs of the expanding bureaucracy.-Oscar Wilde
I mean seriously, you're a caterpillar, and you're immortal
Trust me, Immortality isn't any fun when you live in a glass jar with small air holes punched in its lid...
Of course facts don't matter when fear mongering trumps reason.
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.
thegodmovie.com - watch it
http://www.hss.caltech.edu/~camerer/Ec101/JudgementUncertainty.pdf
Tversky, A. & Kahneman, D. (1974). Judgment under uncertainty: Heuristics and biases. Science, 185, 1124-1130
CC.
TaijiQuan (Huang, 5 loosenings)
http://www.masshightech.com/blog/2009/09/25/antigen-express-synthetic-h1n1-flu-vaccine-in-the-works/
Recode the DNA or RNA to use the slowest, most "pessimal" coding for the same proteins. The virus is externally the same but reproduces orders of magnitude slower, slow enough for the immune system to kill it before it can cause any harm. And the extent of the recoding is such that it's effectively impossible for the virus to revert to pathogenic form.
PHEM - party like it's 1997-2003!
You guys are running around producing Immortal caterpillars and noone let me know? Bastards!
I can't wait for the final showdown where they fight with tiny little katanas and broadswords. It's going to be really tough on the little guys because it's hard to tell if you just cut off your opponent's head or only gave him a free Brazilian Butt Lift... There can be only one.
You have the right to remain sentient. If you give up the right to remain sentient, you will be elected to public office
How many patents on this thing again? I guess the developping countries arent' gonna get it before a while without paying these lab's taxes.
mono = evil
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?
So... we're not talking about the bulldozers? Well consider ME dissapointed. My bulldozer breaks down WAY too much.
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.
First entomology, then virology, and finally bioinformatics systems. Bugs follow me wherever I go.
I've done some IT contracting work for Medicago for a few years, they're a local enterprise, and I know the people behind the technology and I know their installations quite well. It's quite impressive, and I know they're now set on human testing after years of work and animal tests. Glad to see them getting some attention. I think this kind of technology is the future of medicine production.
If he explores all forms and substances Straight homeward to their symbol-essences; He shall not die.
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.
Where's the "What could possibly go wrong?" tag?
Populus vult decipi, ergo decipiatur...
"Force shits upon Reason's back." - Poor Richard's Almanac
Most(all?) viral enveloppes are self assembling and do not need to be hybridised with the vector on a protein level. You just have to make sure your env proteins are expressed trough the vector, so you end up with infected cells bursting with empty shells (as not viral content is produced). You could still have some vector particles in the raw yield, but you need to purify it anyway. Lastly, what negative effects would you expect from an immune reaction to either a plant or insect virus? On the contrary, most vaccines employ adjuvants to make the immune response stronger, so contamination with vector particles would probably not reduce the efficiency of the vaccine.
This space is intentionally staring blankly at you
It's a joke. I guess it looks like a troll when abbreviated, but really, you should read the entire comment before modding.
i am aware of how vaccines work
i just dont trust this latest batch that has and is being rushed to market over the H1N1, i will take my chances without this vaccine.
Politics is Treachery, Religion is Brainwashing
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.
This space is intentionally staring blankly at you
No, i did not watch this 'I am legend' thing you talk about. What is it, a painting or something?
This space is intentionally staring blankly at you
The goal is to make a Very Hungry Caterpillar.
Sure, after all it is just a different flu. However, the statistics who dies from it suggest that a strong immune system is an extra risk, the deaths are not in the age categories you would expect with a normal flu.
But your decision seems to be based on scary stories, and fear is not a good advisor in general and neither is stubbornness. Your call, Darwin may take care of you...
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You will off course have those 'good rna' sequences ready and are willing to be the first test subject? Why not?
BTW: those empty particle may very well not contain the actual proteins needed for infection, as only the H&N proteins offer enough protection. So any rna inside the particle will never be injected.
This space is intentionally staring blankly at you
its too late for a darwin award, i have been a father of two boys. i left the choice up to their mom to manage their vaccines. besides they only ask me for money
Politics is Treachery, Religion is Brainwashing
If they release the particles under the GPL, would that square their viral properties or just double them?
Open Source: I'll show you mine if you show me yours.
i am aware of how vaccines work
i just dont trust this latest batch that has and is being rushed to market over the H1N1, i will take my chances without this vaccine.
This "latest batch" has been almost six months in the making, which is roughly the same length of time it takes to develop the seasonal flu vaccine each year. Flu already requires a new vaccine every year: different strains require different vaccines, and every new year brings one or more new strains of flu, and this year's swine flu vaccine is no different from the vaccine for any other strain of flu in that respect. When a new strain arises, scientists don't have to throw away all their knowledge about making flu vaccines or treat it as a from-scratch research project. The biggest difference this year is that scientists found out about the novel H1N1 after they'd already started work on this year's seasonal flu vaccine, so it was too late to include it. This is why they're running behind on vaccine production.
Some background is required to appreciate this. Flu mutates fairly rapidly, since it's a single-stranded RNA virus. A "strain" is actually hundreds of individual mutant lines inheriting from a common ancestor but with significant differences between them. From the perspective of creating a flu vaccine, two proteins are critically important: hemagglutinin and neuraminidase, "H" and "N" respectively in "H1N1". Both of these proteins are directly involved in the cell-to-cell spreading of the virus — and thus highly conserved across mutant lines, and even across strains — and both of these proteins can be recognized by the immune system on the exterior of the virus. If you create a vaccine for one mutant line, then that single vaccine will be effective against most of the other mutants lines within the same strain. That said, there are other important proteins besides "H" and "N", and these differences mean that a vaccine for one H1N1 strain (e.g. A/Brisbane/59/2007, a target of this year's seasonal flu vaccine) will offer only a tiny amount of protection against any other H1N1 strain (e.g. the new swine flu strain).
Immunity to this year's strain will be widespread by next year, either by vaccination or by infection. This is unfortunate because some other strain (often one that already exists today) will fill the empty niche and become the "new" strain next year, and a new vaccine will be needed to protect against the "new" strain. Happily, scientists can look at this year's epidemiological data and make some pretty good guesses about which strains are likely to infect lots of people. They pick the three to five strains that look positioned to cause the most harm, and they start work on a combined vaccine against all of them for next year's flu season. This happens as the current flu season winds down in late Winter/early Spring, about six to nine months before the vaccine will be needed for the next flu season, because it will take that long to grow the flu viruses in chicken eggs, to kill the viruses, and to make doses of vaccine out of the viral remains.
Once next year's strains have been identified, all the hard research work has already been accomplished: growing the virus in chicken eggs rarely changes from year to year, killing the virus is easy and repeatable (and easy to verify before making a vaccine out of it), and making doses from the dead virus is usually trivial. When complications arise, it's almost always in the viral growth stage. If the strain is strongly bird-associated (e.g. the H5N1 "bird flu" strain from a few years back), the flu strain might kill chicken eggs too quickly. (Thankfully, viruses with this problem rarely spread well from human to human, since the virus must make a trade-off between infecting birds well or infecting humans well.) Alternately, the virus might not grow very well at all in chicken eggs, which is a pretty rare event since chicken eggs have very few defenses and even human-adapted strains usually retain the ability
Range Voting: preference intensity matters
i have been a father of two boys.
When did you ever stop being?