New polio vaccine could eradicate it for good

直到1950年代,小儿麻痹症死亡,数百万人残废。The discovery at that point, by Albert Sabin, of a weakened form of the virus that could be administered by mouth on a sugar lump was a game changer. And by the year 2000 the world was within a whisker of eradicating the disease. But there was a problem: in a small minority of cases, the weakened vaccine form of the virus would mutate and regain its virulence, seeding live polio virus back into the environment. Now scientists think they might have the answer: UCSF’s Raul Andino together with colleagues in the UK has produced a version of the polio vaccine into which they have engineered a number of additional genetic changes, further weakening the virus. Unless it reverts all 5 of these changes at the same time, which is a vanishingly remote possibility, it cannot become virulent again. Data from the World Health Organisation, who have tested these new vaccines, show they work, and suggest they give us our best chance yet of eradicating polio from its final strongholds on Earth…

Raul - In the 50s, there was two vaccines developed. One by Jonas Salk and one by Albert Sabin. Albert Sabin's vaccine was then used for many years to try to control polio myelitis. And the vaccine was very effective but not perfect because it was alive and sometimes could become more strong and could cause the disease itself.

Chris - But we have got killed polio vaccines that we're using in countries like the UK at the moment where we've eliminated the virus. It's not circulating in our country anymore. So we use the killed vaccine. So why can't we just use that everywhere around the world and solve this problem?

Raul - That's a good question. The killed vaccine is very effective to prevent disease, but it doesn't prevent the virus to circulate. It continues being transmitted from people to people in a silent form without causing disease. It's more expensive and you need medical personnel to administer the vaccine because it needs needles. In contrast, the Sabin vaccine, you give it orally and so you don't need a specialised personnel.

Chris - So your challenge then was to try to come up with something with all the virtues and benefits of that Sabin live vaccine that does endow sufficient protection to stop this virus circulating, but doesn't have the problem of the risk of it reverting back to being a transmissible, fully virulent virus capable of causing polio-like symptoms.

Raul - That's exactly right. So the key question here was can we modify the original Sabin vaccine without changing how effective it is and how easy it's to produce and to deliver, but prevent that Sabin vaccine now will acquire those mutations.

Chris - So how did you do that then? How did you change it in such a way that it would have those characteristics?

Raul - What we did is introduce and number of additional mutations in the genome to make the virus to have to go over many more mutations such as single one. The original Sabin vaccine with a single point mutation. You can make the virus as strong as the wild type and that virus could cause disease. And so what we did is introduce mutations that now all of them has to change at once. You need five mutations that needs to be reverted and so the probability for this to happen is much lower.

Chris - So the virus basically would have to change all five of those things all at once, all in the same virus to revert back. Whereas previously it would only have to change one. So the odds of that happening, you are arguing, are so slim that this makes what you've constructed much, much safer. But how did you know where to go? How did you pick on those places in the virus?

Raul - It was two particular things that we did. One is more trial and error and a particular region of the genome that we knew accumulated modifications that were causing the problem. And then the other one was a little bit more rational. We knew that there is a particular enzyme that makes the virus to introduce mutation and we modify that particular enzyme so it doesn't introduce those mutations and that reduced the ability of the virus to evolve.

Chris - And are you confident that having made these changes, you haven't affected the ability to grow the virus sufficiently so we can make vaccines from it? And secondly, when we put those viruses into people, they do the job as well as they did historically.

Raul - So what we did is first look at this in cell culture and in animal models in the lab, and it was very similar compared to the Sabin. Also in people with did clinical trials. And then people also demonstrate that what we call the kinetics of replication was very comparable to the original Sabin.

Chris - And you are confident that the people that have been challenged with this are now protected and will have the same duration of protection against polio for real, that they would've done had they had the original Sabin polio vaccine.

Raul - The World Health Organization, WHO, has used the new vaccine in about 28 countries and after 600 million doses later, we know the vaccine is safe and immunogenic and it has been effective to stop epidemics. So right now it's being used as an emergency measure. Moving forward, I think that is possible that with this vaccine, we replace the previous saving vaccine because it's safer.