ritish scientists say they have developed new viruses to serve as the basis for a safer polio vaccine, a much-needed tool as the world nears the eradication of the disease.
While more research is needed to see if the vaccine strains are safe and effective in people, those involved in the polio eradication effort cheered the report, published Thursday in the journal PLOS Pathogens.
“I’m impressed. I didn’t expect this to happen, certainly this quickly,” said Dr. Neal Halsey, director of the Institute for Vaccine Safety at Johns Hopkins Bloomberg School of Public Health in Baltimore. Halsey was not involved in the research, but serves on a World Health Organization polio research committee with the senior author of the study.
Polio has been brought to the brink of extinction by two vaccines designed in the 1950s by American scientific giants Jonas Salk and Albert Sabin. The polio eradication campaign, which began in 1988, has succeeded in halting spread of polioviruses in all but two countries, Pakistan and Afghanistan.
The vaccines have prevented millions of people the world over from being paralyzed by polioviruses. But for all their history-changing benefits, both vaccines come with significant drawbacks. And even if polio transmissions can be stopped by sometime in 2016, as many hope, the world will continue to need a safe vaccine, potentially for decades to come.
There has been a concerted effort to find a better, safer vaccine, but that goal has been elusive.
Scientists at Britain’s National Institute for Biological Standards and Control, however, reported they have engineered polioviruses that could be used in a next-generation vaccine that would solve the problems of Sabin’s oral polio drops and the risks associated with production of Salk’s injectable vaccine, known in the polio world as OPV and IPV, respectively.
The British team, funded by Britain’s Department of Health, reported it has managed to modify Sabin’s vaccine viruses so that they could be used in an inactivated vaccine, one in which the virus has been essentially killed. In animal testing, the new vaccine viruses appeared to generate a protective immune response.
“It’s really a step in the right direction. They’ve done a nice job,” said Walter Dowdle, a former deputy director of the Centers for Disease Control and Prevention and a member of a working group that advises the WHO on polio vaccine issues.
It has long been understood that neither of the existing vaccines is an ideal option for use when polio transmission has stopped.
Sabin’s oral vaccine, made with weakened polio strains, will on rare occasions paralyze a child who takes the vaccine drops. The WHO estimates that for every group of a million children getting multiple doses of oral vaccine, between two and four will develop polio paralysis from it.
The oral vaccine poses another, more serious problem. Vaccinated children discharge the live, weakened vaccine viruses in their stool. Those vaccine viruses get into the environment, finding their way into other children. As they pass from one to the next, they can lose the mutations that weakened them, regaining the paralytic power of regular polioviruses.
At this point, more children are actually being paralyzed by vaccine viruses than by wild polioviruses. The Global Polio Eradication Initiative says that in 2015, 70 children were paralyzed by polio but 213 were paralyzed by vaccine viruses that regained virulence.
When polio cases numbered in the tens of thousands, the oral vaccine risks were outweighed by the vaccine’s considerable benefits. But it is clear polio will never fully vanish as long as oral polio vaccines are in use, and those vaccines will be phased out when transmission stops.
At the individual level, the injectable vaccine created by Salk is safer, though its higher cost and the need to have it delivered by a health provider have for the most part put it out of reach of many developing countries. (Oral polio drops can be given by anyone with a moderate amount of training.)
But production of the injectable vaccine poses its own risks, which will become even greater once polio transmission ceases. To make the vaccine, manufacturers must generate large volumes of polioviruses — and these are not the weakened versions — which are eventually killed and formulated into vaccine.
If a production plant had an accidental leak, the results could be disastrous — especially if it were to happen in a country where polio vaccination efforts had lagged and large numbers of children were not protected against polio. That’s not just a theoretical threat; a GSK production facility in Rixensart, Belgium, accidentally released 11 gallons of solution containing live polioviruses into nearby waterways in 2013.
It is also feared these supplies of virulent polioviruses could be targets for would-be bioterrorists.
The vaccine viruses engineered by the British team, led by veteran polio researcher Philip Minor, will be safer than wild polioviruses, because like Sabin’s vaccine viruses, they are weakened. But unlike Sabin’s versions, the new vaccine viruses can be used in killed form, so there is no concern they will paralyze the immediate recipient. Nor can killed viruses spread from child to child, regaining virulence.
“This is a very important step in terms of trying to have viruses that can be used to produce vaccine without any risk of those viruses causing outbreaks of polio,” Halsey said. He and others noted, though, that more work needs to be done to prove that the new vaccine viruses will deliver on their promise when used by people.
And it remains to be seen if the vaccine viruses will actually ever be produced, experts acknowledged.
Polio eradication program leaders hope that 2016 will be the year when polio transmission finally stops. Cessation of transmission would be followed by a three-year certification period, in which heightened surveillance would tell the world whether polio was truly gone. If no additional cases were seen, polio could be declared eradicated in 2019.
The Global Polio Eradication Initiative’s strategic plan says countries should continue to use the polio vaccine — and it will have to be the killed virus vaccine — for at least five years after eradication is completed. Developed countries are unlikely to stop vaccinating for years, maybe decades. But some countries with limited health budgets and multiple health problems will want to stop vaccinating when it’s considered safe, Dowdle said.
So will manufacturers take on the substantial expense of testing and licensing a wholly new polio vaccine for a market that is bound to start shrinking? Even if all goes well with these vaccine viruses, it could be a decade before a vaccine containing them is ready for use.
This is a critical issue, admitted Dr. Walter Orenstein, associate director of the Emory Vaccine Center at Atlanta’s Emory University and a consultant on polio for the Bill and Melinda Gates Foundation.
“If this is going to be a viable tool, there needs to be a commercial incentive for use,” he said. “Would a five-year use be adequate commercial incentive to go through all of the development phases?”