Tuesday, April 08, 2008

Building a better polio vaccine (or any vaccine, really)

I cant imagine being a physician 60 years ago, with this picture being an every-day reality:
Row after row of kids with paralyzed diaphragms, locked in iron lungs. Polio.

Though I suppose I cant be too 'shocked and awed'-- I get this:
Yaaaaaay......

*sigh*

But with gymnasiums of iron lungs existing only as fading memories for some, and just pictures in history books for others, its easy to forget one tiny little fact-- Polio still exists, in the wild, on this planet. Unlike smallpox, which is confined to prison in a few research laboratories, we have not eradicated polio. And we might never get rid of it completely, unless we change our vaccine strategy.

You all might be aware of three different kinds of vaccines:

  1. Only a component or protein of a virus/bacteria, like a tetanus shot. No risk of infection at all.
  2. A dead virus/bacteria, like your annual flu shot. No risk of infection at all.
  3. An attenuated virus (has been passaged over and over in a different species so its crippled in humans, evolution, WHOOO!). Might actually get the disease from the vaccination.
Polio vaccines come in two forms, Numbers 2 and 3. I got the live attenuated one on a sugar cube before I started school. It provides the best protection because lots of branches of our immune system are activated by the 'live' vaccine. Our immune system can then remember what worked best if we are ever confronted with a real polio virus. I know this one is also preferred in developing countries, as its super easy to administer. Sugar cube. No needles to sterilize. Yay!

So why isnt polio gone?

A problem with this attenuated vaccine is that you poop polio viruses. Crippled polio viruses, but you poop viruses. And because polio is an RNA virus, it might have mutated back to a wild type form.

Crap.

What can we do? We dont want to keep giving the oral vaccine because it keeps polio 'alive'. We cant do the dead vaccine because its just not as good, and impractical in areas that need the most help. And we cant not give vaccines.

Vignuzzi et al think they have a good idea for how to keep the better live vaccine for RNA viruses, and lose the crappy wild-type polio pooping-- Controlling the attenuation process:
Engineering attenuated virus vaccines by controlling replication fidelity

Their idea is simple-- alter the viruses ability to mutate by making its RNA dependent RNA polymerase better! They tested lots of different amino acid positions and lots of different replacements to see what mutation they could make that would not hurt the overall fitness of the virus. If you start messing with an organisms fitness, you are putting it under pressure to mutate. So dont mess with it! Let it replicate nice and happy, no problems, no stress, let it replicate.

Why? So your immune system can launch a full on assault on the progeny virions, giving you that awesome attenuated vaccine response!

And those progeny viruses (you will still be pooping them, but not as much according to this paper), will be under no pressure to mutate away from the vaccine strain, and their ability to do so will be handicapped anyway (its hard to mutate when your polymerase is super accurate!), so you lose (or at least lessen) the chance of pooping a wild-type virus back into the environment.

Neato! This directed attenuation scheme could work on any RNA virus-- measles, mumps, rubella, rabies-- but they havent actually tried this yet. I mean, they tried it in mice, and got great results, but they havent tried it in people, much less an entire population.

Its nice to know that even though you and I can live blissfully ignorant, iron-lung-free lives, someone is out there making sure our kids can have the same luxury. And theyre using basic principles of the theory of evolution to do it. *gasp!*

26 comments:

Corey Smith said...

That is one neato idea!

Daniel said...

I remember getting my smallpox vaccination in the military. Bit of a hassle, really, since it's a "live-virus" injection. . .the injection site had to be kept clean, but touching it made for a risk of spreading the infection to other points of the body. Hard to deal with in a war-zone.

If you don't mind speculating on this point, do you suppose that this technique could be used to make this vaccine easier to deal with?

J Myers said...

If you start messing with an organisms fitness, you are putting it under pressure to mutate.
Shouldn't this be "you are putting it under pressure to evolve"? I thought mutation itself was random.

Wanderin' Weeta said...

That first photo brought back memories. Not good ones.

I am old enough to remember the dread we felt anytime we, or anyone we knew, was a bit "under the weather". Was it polio? So many kids were sick, so many dying.

My brother got it, in the late 1950s. It was a very mild case, but he still has reduced motor function.

The anti-vaccers have no idea. If they knew the tiniest scrap of history, they would have their kids in for their vaccinations at the first opportunity.

nqdrstu said...

If you start messing with an organisms fitness, you are putting it under pressure to mutate.
Shouldn't this be "you are putting it under pressure to evolve"? I thought mutation itself was random.


Evolution would be the step after mutation, where the organism's offspring inherit a beneficial series of mutations.

maxi said...

Great post ERV! I like learning science first thing in the morning, and it's nice to brush up on a subject that I have kinda forgotten about. Yay for science!

Christophe Thill said...

Sorry, this is a bit of a statistician's rant about methods and stuff. I know it can seem small compared to the fact that people are dying and all. But when I look at the HIV map, I really, really wonder how the authorities of Greenland managed to have such a small number of HIV infected people. They must truly have a terrific prevention policy.
(Or perhaps just a small population?)

Sili said...

The entire population of Greenland is only about 50k. I wouldn't be surprised, though, if they have a higher relative incidence than the rest of Denmark. They still suffer badly from the colonialism. They have a dreadful degree of alcoholism. Child abuse runs rampant.

Thank you, Abbie, I feel I learnt a lot from this post. A friend of my parents suffered polio and he was much handicapped from in later years. Died from lungcancer, though.

Anonymous said...

I might be wrong, but I thought part of the reason for using the attenuated virus vaccine was that the virus was shed by the person inoculated. That way you might expose unvaccinated people nearby to the vaccine strain and thus immunize them against wild-type polio as well.

Iron Soul said...

But if the virus you are shedding had mutated back to the wild strain, wouldn't that be bad?

William Wallace said...

This recent polio outbreak was caused by a child who was infected by a supposedly "attenuated virus" vaccine.

Attenuated vaccines are less expensive, and are used in other countries. The infected child had been vaccinated in another country, and came to the U.S. to infect unvaccinated Mennonite children.

Is it possible that the attenuated virus evolved back into an unattenuated version?

In any event, the photo is scary, but one might imagine that polio antiviral drug development could mitigate consequences of polio infection. As far as I know, none of the Mennonite children ended up in an iron lung.

Dr. Duke said...

If I recall correctly, the attenuation process for polio was done before we knew much about genetics, and the attenuated strain has something like 2 base changes in its whole genome from wild type.

With what we know about genetics today, it should be trivial to engineer an attenuated strain with 20 or more mutations and hence almost zero chance of reverting to wild type.

I get the impression that the root of the problem is not a lack of ability to make a safe polio vaccine, but a lack of financial incentive to do so. It costs too much to get the new safer vaccine FDA-approved, and the resulting product would not generate any more money than the currently approved product.

Olorin said...

So.... Why does your post not carry the logo for "Blogging about peer-reviewed publications." It should.

I too am old enough to remember iron lungs and shutting down public swimming pools every August. And I have several friends who now suffer from "post-polio syndrome"---not as severe as polio itself, but still a grim reminder that we haven't yet left polio behind, even in the US.

William Wallace said...

"I get the impression that the root of the problem is not a lack of ability to make a safe polio vaccine, but a lack of financial incentive to do so. It costs too much to get the new safer vaccine FDA-approved, and the resulting product would not generate any more money than the currently approved product."

I agree. I also suspect that the reason we had thirmisol was motivated by cost.

And the reason the CDC is stonewalling Mark Geier on the post-thirmisol incidence of neurological disorders has more to do with preserving the faith and credit given to the CDC by the American people than science.

This was an interesting article: Autism Rates Drop After Mercury Removed From Childhood Vaccines

Richard said...

Creationists, of course, will argue that it's not evolution, because...

o They're still JUST VIRUSES!!!
o It doesn't generate any "new information" (whatever that means)
o Then why are there still apes?
o Since this involved scientists deliberately designing a better vaccine, it's actually INTELLIGENT DESIGN!
o Hitler! Nazis!
o A vanishing fraction of scientists, most of whom weren't actually biologists, signed a mealy-mouthed petition that doesn't actually disagree with the theory of evolution
o I'll laugh when you burn in Hell

Anonymous said...

Sorry, this is a bit of a statistician's rant about methods and stuff. ...

I was thinking along similiar lines: When is the standard for such maps going to be area-equalized for population, and where is the map that shows the rate of infection?

-Rusty

Maggie Rosethorn said...

W Wallace...if you want to post about peer reviewed articles, something in Journal of American Physicians and Surgeons ISN'T the place to refer to. They are not considered a peer review journal. (Check Quackwatch or Respectful Insolence for more info about JPANS).

And as for the Geiers...well, I suppose quacks have their rights too.

Tyler DiPietro said...

This was an interesting article: Autism Rates Drop After Mercury Removed From Childhood Vaccines.

Whenever anostensible "medical" story cites anything from JPANDS, it should send up a red flag, for many reasons.

Bill said...

The picture brings back bad memories. As a kid the number one fear was to end up in an Iron Lung.

It was a terrifying prospect. Kids in my school who had polio walked around wearing huge, metal leg braces and crutches. Those were the "lucky" ones.

The Salk polio vaccine completely eliminated the fear of polio from public consciousness. What was a nightmare for me never affected my kids in the slightest.

Unless you lived in the 50's you have no idea how scary the word "polio" was.

Maggie Rosethorn said...

Thanks for the links, Tyler. I have lots of trouble with HTML and links so am always thrilled when someone with the ability to do so helps me out!

Tyler DiPietro said...

"Thanks for the links, Tyler. I have lots of trouble with HTML and links so am always thrilled when someone with the ability to do so helps me out!"

You are very welcome. :)

William Wallace said...

I am considering the POVs expressed in various blogs, but JPANDS is peer reviewed, unlike most blogs.

Tyler DiPietro said...

"...but JPANDS is peer reviewed..."

If by "peer" you mean someone who conforms to the stated ideology of the journal and its parent organization. Otherwise, to call it "peer-reviewed" in any standard scientific sense is a joke.

Joshua said...

The idea of adding an essentially new version of RNA polymerase into the wild bothers me slightly. If this spread to other viruses you might have viruses in general mutating less especially because from a gene-centric perspective a more accurate RNA polymerase might have a decent survival chance because it replicates itself more accurately even as it makes their be fewer mutations overall. I don't know if this is a serious concern and I don't see any immediately problems that would be caused by this sort of issue but it may be worth thinking about.

fahrschule w├╝rzburg said...

Good Job! :)

Mona Albano said...

The image is here: Iron Lung ward