The world is closer than ever to eradicating polio, the horrible paralysis-inducing disease that primarily infects children. But the tail-end efforts are at risk from the very thing that made eradication programs a success: the vaccines themselves.
"Sooner or later you get to the point — in theory you get to the point — where all the [polio] cases in the world are caused by the vaccine," Philip Minor, the head of virology at National Institute for Biological Standards and Control in the United Kingdom, says. "So you are basically using the vaccine to protect against the vaccine. And that is just ludicrous, isn’t it?"
The difference between the number of cases of wild-type polio and the number of vaccine-derived cases is narrowing. In 2015, according to the Polio Eradication Initiative, there were 70 cases of polio across the globe from wild strains of the virus. There were 26 cases of vaccine-derived polio.
If the world truly wants to eradicate polio, leaving the risk of infections from vaccines is not acceptable.
There are polio vaccines that have made this possible. And they both pose — very small, but significant — risks to global eradication.
The World Health Organization's polio eradication program, which began in 1988, has been one of the greatest success stories in global health. At its peak in the middle of the 20th century, polio killed half a million people every year. In 1988, there were more than 125 polio-endemic countries. Now there are two: Afghanistan and Pakistan. It's not far-fetched to say that very soon, the world will see its last polio case.
That success is due to two great inventions: the oral polio vaccine (created by Albert Sabin) and the injected polio vaccine (created by Jonas Salk). Each has some inherent flaws.
The oral vaccines (OPV) are more effective — but they also contain a live virus
In the 1950s, Sabin noticed that not all strains of poliovirus infected monkeys when exposed. He was able to isolate these strains — and prove they wouldn't infect humans — and form them into a swallowable serum that could be easily distributed the world over. The vaccine is so particularly effective because it first immunizes the gut, where polio takes root in the body.
Because it's five times less expensive than the injected vaccine, and so easy to administer, the Sabin strain became the favored vaccine of the World Health Organization in its eradication efforts. There's no doubt: The world is this close to eradicating polio because of the oral vaccine. Some 3 billion children have received it.
The vaccine's risk: It contains a live virus, which can mutate back into a virulent form.
"Very quickly after you take the vaccine, [oral-vaccine viruses] revert" to a dangerous form, Vincent Racaniello, a Columbia professor of microbiology and immunology, says. This typically isn't a problem, since by the time they become virulent, a person — and his or her surrounding community — is immune. "But for some reason, one in 1.5 million kids who get the vaccine get paralyzed," he says. That number is tiny, but not insignificant.
These vaccine-derived polioviruses also cause new outbreaks in communities that have spotty immunization coverage. A person can shed a vaccine-derived virus for a few weeks. "It's happened over and over," Racaniello says. "We have to stop using OPV as soon as possible. As long as we're using it, we're introducing reverted strains into the environment."
The last wild version of type 2 poliovirus was seen in India in 1999. But a few dozen people contract vaccine-derived type 2 polio in small outbreaks every year. The US phased out oral vaccines in 2000, after the CDC recognized it was causing more cases of polio than the wild-type virus itself in this country.
The WHO plans to phase out the oral vaccine as eradication nears. But it has already taken one step toward that goal. This past April, 155 countries switched over to use an oral vaccine no longer immunize against type 2 polio.
(In case one of these Type 2 vaccine-derived strains does start circulating after the vaccine switch -- via someone who gotten the old vaccine containing type-2 -- there's a global stockpile of 500 million doses of a Type 2 vaccine ready to deploy)
All oral vaccines will be (ideally) phased out by 2020, as injected vaccines — which are more expensive and more difficult to administer — become the standard.
The injected vaccines contain dead viruses and are safe, but are manufactured from very virulent strains. And accidents can happen.
When Salk invented the injectable polio vaccine in the early 1950s, it was the first preventive treatment for the disease. The formula remains essentially the same today: The vaccine is made from large amounts of live, dangerous polioviruses that have been killed (inactivated, as the scientists say). These vaccines pose no risk of infection.
The risk with these vaccines is in manufacturing. If that live, deadly poliovirus somehow spills out of the production facility, it could recirculate. Accidents have occurred before. In 2014, a GlaxoSmithKline facility in Belgium released 45 liters of concentrated poliovirus into the local sewage system.
The containment risk is no different for polio than for other vaccines made by this process, like the flu vaccine. But if total eradication is the goal, this bug really shouldn’t exist in a dangerous form anywhere. "If you've got rid of natural polio and then release a load of virulent virus, the consequences are greater," Minor says.
The injected vaccine is also slightly less effective than the oral vaccine, as it does not immunize the intestine. People with the injected vaccine can carry polio in their guts without getting sick.
Replacing oral vaccines won't be so easy
The most obvious solution to combat vaccine-derived polio is to replace the oral vaccine with the injected vaccine world over, which the WHO intends to do.
But this also poses a major dilemma. If all oral vaccines are halted tomorrow, and replaced with injected vaccines, then the vaccine-derived strains will still circulate.
That's because the injected vaccine doesn't immunize the intestines, where the vaccine-derived strains reproduce and thrive. People wouldn't get sick, but they'd still carry the virus. "It could spread forever," Racaniello says. That's the scenario I worry about."
Then, if the world gets complacent and stops immunizing kids with the injected vaccine, these oral vaccine-derived strains could make a big comeback.
"We're going to need [inactivated] vaccines in the world for many years to come, but we don't know how long that is," says Yvonne Maldonado, a Stanford professor of pediatric infectious diseases who is currently studying how long these vaccine-derived strains can circulate in a community.
There are also people who excrete poliovirus for decades without showing symptoms — like Typhoid Mary. These people bodies have a slightly weakened immune system. They can't get rid of all of the polio virus, but they also never succumb to it. "We've got one in this country [the UK] who has been going for 28 years," Minor says. "I think you couldn't stop vaccinating while this man is still there excreting the virus."
Minor is looking to shake up the status quo. Last December, he and his colleagues at NISBC published a paper in PLOS Pathogens, outlining a newly engineered viral strain to make vaccines. It solves a lot of the problems inherent in the vaccines today.
Minor took the Sabin strain and then altered a specific area of its RNA (genetic code) to make it much less prone to revert back to a deadly form. (Minor's viruses also don't appear to be able to grow in a human gut, which is essential for stopping the spread of vaccine-derived polio.)
He suggests his new strain can also be inactivated and fashioned into an injectable vaccine. "What we're aiming at is that a manufacturer can take a strain and grow it up, and even if the plant blows up, there's no risk," Minor says.
Maldonado, who is familiar with Minor's work, says it's a great idea. "We want to make sure that we have more than one plan-b in our back pocket," she says.
Racaniello's doubtful such a strain will come into production. There are economic pressures — taking a new vaccine to market involves a lot of money — but it also might be too late for the polio eradication effort.
"You cannot use these strains without testing them," Racaniello, who edited Minor's paper, says. "And they have to be shown to be efficacious. How can you do that when there's hardly any polio left? ... I think it's too late."
Overall, the researchers I spoke to are optimistic polio eradication is imminent, but say vaccine research still needs to continue.
"There aren't many people doing research in this area because I think most people feel that polio is simple," Maldonado says. "There's two vaccines, you just give them to everybody and we'll just get rid of polio." It's a lot more complicated than that.