After decades of work and mass vaccination campaigns that have spared millions of children from paralysis, the world is close to wiping out polio.
But a small number of outbreaks that have simmered in areas of low vaccination remain. And some happened after weakened virus in the oral polio vaccine, over time, moved around a community and regained the ability to cause disease. No other vaccines made with weakened live viruses have caused outbreaks of disease.
To stamp out vaccine-derived polio outbreaks, the World Health Organization has granted emergency use for a new polio vaccine. The oral vaccine got the go-ahead on November 13.
“We are very, very enthusiastically looking forward to using this new vaccine,” says medical epidemiologist Chima Ohuabunwo of Morehouse School of Medicine in Atlanta, who has worked on polio eradication in Africa for more than two decades. Along with continuing the crucial work of improving vaccination coverage in places where it is low, the new vaccine will “hopefully … take us to the finishing line of polio eradication.”
Eight years after the WHO’s 1980 declaration that the world was free of smallpox, the Global Polio Eradication Initiative launched to tackle polio. The disease was a promising candidate for eradication. An effective, easily administered and cheap vaccine was available. And poliovirus, which naturally infects only humans, doesn’t hang around in other animals in between outbreaks.
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Most people who become infected with poliovirus don’t feel sick, while some have flu-like symptoms. But about one in 200 become paralyzed for life. Although not a routine threat in the United States since the early 1950s (SN: 9/12/19), polio has continued to harm people, especially children, around the world.
In the late 1980s, wild poliovirus paralyzed more than 1,000 children each day, according to the Global Polio Eradication Initiative. Since then, thanks to widespread vaccination campaigns, cases have plummeted by more than 99 percent, and two of the three types of wild poliovirus have been eradicated. The last cases from type 2 and type 3 were reported in 1999 and 2012, respectively. Only wild poliovirus type 1 remains, and only in two countries: As of December 30, 56 cases were reported in Afghanistan and 83 in Pakistan caused by type 1, in 2020.
Much of this progress has been possible because of the oral polio vaccine. “It’s been the workhorse of the eradication campaign,” says virologist and infectious disease physician Adam Lauring of the University of Michigan School of Medicine in Ann Arbor. Immunization with the oral vaccine has prevented more than 13 million cases of polio since 2000, according to WHO.
A big advantage of the oral vaccine, which is made of live but weakened poliovirus, is that it not only protects against paralysis — it also can stop wild poliovirus from spreading in a community. Poliovirus moves from person to person when someone ingests water or food contaminated with virus-containing stool. The oral vaccine prevents wild poliovirus from multiplying in the gut and being passed on. (There is another, more expensive, injected polio vaccine with killed virus that prevents paralysis but not viral spread.)
While the oral vaccine has nearly wiped out wild poliovirus, it has a vulnerability. Weakened poliovirus in the vaccine has genetic changes that keep it from causing disease. As vaccine virus multiplies in the gut, it can lose key genetic changes, bringing it closer to behaving like wild poliovirus. And altered vaccine virus “can be spread to others and establish community transmission,” says biologist Raul Andino of the University of California, San Francisco School of Medicine. That can be a problem if not enough people have been immunized against polio.
More than 80 percent of children need to be vaccinated to keep poliovirus from spreading in a community. The first vaccine-derived polio outbreak to be detected occurred in the Dominican Republic and Haiti two decades ago, in areas with low vaccination. That allowed altered vaccine virus, shed in the stool of the immunized, to spread largely unchecked and, over time, return to a form that causes paralysis (SN: 8/10/04). The full process of vaccine virus reverting to disease-causing virus is rare and takes many months of moving around a community.
Today, vaccine-derived outbreaks are primarily found in Afghanistan, Pakistan and countries in Africa. Most of these outbreaks — which have been responsible for more polio cases in the last few years than the remaining type of wild poliovirus — are linked to vaccine virus type 2. Vaccination campaigns, which had used an oral vaccine containing weakened versions of all three types of poliovirus, switched to using a formulation with just types 1 and 3 in 2016.
However, the way to stop a type 2 vaccine-derived outbreak is with an oral vaccine containing only the weakened type 2 virus. And that has sparked new outbreaks, researchers reported in Science in April. “It is this vicious circle,” Lauring says. As of December 22, in 2020 there were 854 polio cases linked to the type 2 vaccine virus.
Hence the quest for a new and improved poliovirus type 2 oral vaccine, one that kept the good parts of the original but with tweaks to try to prevent problematic genetic changes. “It’s a wonderful vaccine, so we didn’t want to change the characteristics” that induce the body’s immune response, Andino says. “The only thing we wanted to do is prevent the reversion” to a disease-causing virus.
Andino and colleagues modified the type 2 vaccine virus in several places. The researchers altered a part of the virus’s genetic instruction book, or genome, to make the virus less likely to develop a “gatekeeper” change: a first, critical step along the road to regaining the ability to cause disease.
Poliovirus can swap pieces of its genome with related viruses called enteroviruses. So the researchers moved a string of genetic letters the virus needs to make more copies of itself close to the “gatekeeper” modification. That way, if the vaccine virus was able to ditch that modification by way of a swap, it would lose this necessary string of genetic letters too, and die out.
Finally, the team tinkered with an enzyme that RNA viruses, including poliovirus, use to help replicate themselves. The enzyme is sloppy and can introduce a lot of genetic changes, Andino says. That’s advantageous for the viruses, which “are continuously trying to adapt to a new environment,” he says. Andino and colleagues modified this enzyme in the vaccine virus to introduce fewer mistakes, “so the virus cannot evolve so quickly.” The researchers described their improved oral polio vaccine in a study in Cell Host & Microbe in May.
The new oral polio vaccine was shown to be safe and to produce an immune response similar to that seen with the original vaccine in infants and children, researchers reported online December 9 in the Lancet. The hope is that the modifications will slow the evolution of the new vaccine virus such that it can end the existing outbreaks without creating new ones.
The vaccine-derived outbreaks are a significant, yet surmountable hurdle to polio eradication, says Ohuabunwo, and “science is helping.” But the key to ending polio is “very high vaccination coverage.” Obstacles including war, migrating populations, difficult terrain and lack of vaccine acceptance have created pockets of inaccessible children, he says.
Reaching all children requires engaging community leaders, providing culturally sensitive information and finding out how to meet other community needs, says Ohuabunwo. For example, while working in Nigeria, he and his colleagues made progress with nomadic populations. It meant “sometimes combining vaccinating their children with vaccinating their animals.” The nomads’ cattle would be immunized against brucellosis and anthrax bacterial infections. Protecting the animals also protected the nomads from these infections, he says, and motivated their cooperation towards having their children receive polio vaccine: “a win-win.”
Polio eradication has been a long journey, “but we’re getting close,” Ohuabunwo says. The new oral polio vaccine “is another light in the tunnel.”