Building a better polio vaccine: Revisited

Last year I wrote about a cool paper, arguing for the creation of a new polio vaccine.

Briefly, polio is an RNA virus, thus has an error-prone RNA-RNA polymerase, thus acts like a quasispecies like HIV-1. Now, a live attenuated polio vaccine is the ‘best’ because you activate lots of branches of your immune system, which ‘remember’ the polio virus for a really long time. But because of polios potential genetic diversity, the attenuated vaccine variant can revert back to the wild-type variant, which is ‘more fit’.

This doesnt matter to you, because youve been vaccinated. But if you shed wild-type virus in your poop, and someone who hasnt been vaccinated or is immunocompromised comes into contact with your poop, they get sick (if you think you dont eat anyones poop, google ‘norovirus’).

Vignuzzi et al found they could generate polio viruses that:

  • Had a higher-fidelity RNA-RNA polymerase, cutting mutation rates by half or more
  • Were almost equally ‘fit’ to wild-type virus, reducing selective pressure to revert
  • Did not infect the brain/cns
  • Were still susceptible to anti-polio antivirals
  • Provided better protective immunity to wild-type polio than even the current ‘live’ polio vaccine

They figured out the recipe for a pretty sweet polio vaccine. Unfortunately, its hard to push something like this through clinical trials when vaccines are not ‘money makers’, and we already have polio vaccines that ‘work’.

Why do I bring up this story again?

1. Google News alerted me to an immunocompromised individual in Minnesota who died last month, who was infected with polio (dunno if he/she died of polio complications). The Minnesota Department of Health thinks he/she got it from a shedding immunized individual. If that person had been immunized with a non-neurotropic polio vaccine, this wouldnt have happened.

2. Larry and TR are poo-pooing an idea put forth to decrease insecticide resistance in mosquitoes. This is the one time Im going to disagree with those two guys, cause I think the Read et al are on to a great idea thats certainly worth trying. Current insecticides are fast acting, thus give a strong reproductive advantage to insecticide resistant bugs– whoever can ignore the insecticide can have more babbys, who are also resistant to the insecticide, thus grow up to has lots more insecticide resistant babbys, and so on. Reads idea to relieve this selective pressure? Kill old mosquitoes. Older mosquitoes have already produced several rounds of offspring, but the malaria they are carrying hasnt ‘matured’ yet.

Reads ideas reminded me of Vignuzzis strategy with polio– level the reproductive playing field between the wild-type strain and the vaccine strain, or the resistant mosquitoes and the nonresistant, and you can ‘keep’ the phenotype you want around longer. If there is no reproductive advantage to insecticide resistant mosquitoes, they wont eventually ‘out compete’ non-resistant bugs. By chance they might out compete the non-resistant guys. Or malaria might figure out a way to mature faster in mosquitoes. But I believe Reads approach will buy us valuable time to develop new anti-malarial strategies.

I dont think Larry and TR should be poo-pooing this idea. It is better than our current methods.

Comments

  1. #1 TR Gregory
    April 15, 2009

    I think it’s a fine idea. But is it “evolution-proof”?

  2. #2 Yeshivish Atheist
    April 15, 2009

    Thanks for posting this, the article looks interesting so far. My initial reaction thus far is that I think it may be a successful idea at reducing the selective pressure, but I also share TR’s skepticism in regards to eliminating the selective pressure for the mosquito’s evolution altogether.

    Also, there may be an issue with the selective pressure this may induce on the actual parasites (select for parasites that become infective earlier?) and not just the mosquitoes.

    Regardless, it sounds like an idea worth trying. There are many thoughts running through my mind, but I want to finish reading the article before I post them.

  3. #3 Dunbar
    April 16, 2009

    In terms of a public health viewpoint, I think continuing and expanding use of IPV is better than any sort of attenuated vaccine if one’s end goal is complete eradication. Moreover, attenuated vaccines don’t work too well with immunocompromised people (i.e. HIV infected people) who happen to be heavily concentrated in areas of the world where polio happens to be endemic.

  4. #4 Dan Gaston
    April 21, 2009

    If you are interested in that Abbie this is a paper that came out in science in June of last year:

    http://www.sciencemag.org/cgi/content/full/320/5884/1784

    This was about manipulating codon pair biases through the entire genome of polio to make attenuated viruses. Because lots of small mutations produce the large result the risk of back mutations is minimal. Very interesting work.

  5. #5 Matthew Ackerman
    April 22, 2009

    TR: I think it’s a fine idea. But is it “evolution-proof”?

    Absolutely not. It might not even be particularly ‘evolution-resistant.’ But still, I haven’t looked at the Data, and that is the final arbiter in things like this.

    I don’t remember if I read this some where or came up with it myself, but I vaguely recall an even better idea (IMHO). Mosquitoes have an immune system and malaria is a parasite from the perspective of mosquitoes as well. So, rather than killing mosquitoes (which politely pollinate many of our flowers, thank you very much) why not HELP the mosquitoes by curing the mosquitoes of malaria? Of course, I have no idea how hard it would be to engineer malaria resistant mosquitoes, but if it were possible, it should permanently eliminate malaria, since there would be NO SELECTIVE pressure for the mosquitoes to be vulnerable to malaria infection.

  6. #6 Matthew Ackerman
    April 22, 2009

    whoops! wrong thread. Sorry.

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