After decades of hard work and mass vaccination campaigns that have saved millions of children from paralysis, the world is about to end polio.
But there are still a small number of outbreaks that lead to simmering in low-vaccination areas. And some happened after the virus weakened in the oral polio vaccine, over time, moved into a community and regained the ability to cause disease. No other vaccine made with weakened live viruses has caused disease outbreaks.
To eliminate vaccine-derived polio outbreaks, the World Health Organization has granted emergency use of a new polio vaccine. The oral vaccine was approved on November 13.
“We look forward to using this new vaccine with great enthusiasm,” says medical epidemiologist Chima Ohuabunwo of Atlanta’s Morehouse School of Medicine, who has worked on polio eradication in Africa for more than two decades. Along with continuing the crucial work of improving vaccine coverage in places where it is low, the new vaccine "hopefully … leads us to the goal of polio eradication."
Eight years after the 1980 WHO declaration that the world was free of smallpox, the World Polio Eradication Initiative was launched to combat polio. The disease was a promising candidate for eradication. An effective, easy-to-administer, and cheap vaccine was available. And poliovirus, which naturally infects only humans, does not hang in other animals between outbreaks.
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Most people who become infected with poliovirus do not feel sick, while some have flu-like symptoms. But about one in 200 is 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 every day, according to the Global Poliomyelitis Eradication Initiative. Since then, thanks to widespread vaccination campaigns, cases have fallen by more than 99 percent and two of the three types of wild poliovirus have been eradicated. The last type 2 and type 3 cases were reported in 1999 and 2012, respectively. Only type 1 wild-type poliovirus 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 due to the oral polio vaccine. “It was the workhorse of the eradication campaign,” says virologist and infectious disease doctor Adam Lauring of the University of Michigan School of Medicine in Ann Arbor. Oral vaccine immunization has prevented more than 13 million cases of polio since 2000, according to the WHO.
A great advantage of the oral vaccine, which is made from live but weakened poliovirus, is that it not only protects against paralysis, but can also prevent the spread of wild poliovirus in a community. Poliovirus moves from person to person when someone ingests water or food contaminated with feces that contain viruses. The oral vaccine prevents wild poliovirus from multiplying in the gut and being transmitted. (There is another vaccine against polio that is injected, more expensive, with dead virus that prevents paralysis but not viral spread).
Although the oral vaccine has almost wiped out the wild poliovirus, it has a vulnerability. The weakened poliovirus in the vaccine has genetic changes that prevent it from causing disease. As the vaccine virus multiplies in the gut, it can lose key genetic changes, bringing it closer to behaving like the wild poliovirus. And the altered vaccine virus “can spread to others and establish community transmission,” says biologist Raul Andino of the University of California, San Francisco School of Medicine. This can be a problem if not enough people have been immunized against polio.
Rebecca Martin / CDC
More than 80 percent of children need to be vaccinated to prevent the poliovirus from spreading in a community. The first polio outbreak derived from the vaccine that was detected occurred in the Dominican Republic and Haiti two decades ago, in areas with low vaccination. This allowed the altered vaccine virus, shed in the feces of the immunized, to spread largely out of control and, over time, return to a form that causes paralysis (SN: 8/10/04). The complete process of the vaccine virus returning to the disease-causing virus is rare and takes many months to move around a community.
Today, outbreaks of the vaccine are found mainly in Afghanistan, Pakistan and African countries. Most of these outbreaks – which have been responsible for more cases of polio in recent years than the rest of the wild poliovirus type – are related to the type 2 vaccine virus. Vaccination campaigns, which had used an oral vaccine containing weakened versions of the three types of poliovirus, went on to use a formulation with only types 1 and 3 in 2016.
However, the way to stop an outbreak derived from the type 2 vaccine is with an oral vaccine that contains only the weakened type 2 virus. And that sparked new outbreaks, researchers in Science reported in April. “It’s this vicious circle,” Lauring says. As of December 22, 2020, there were 854 cases of polio related to the type 2 vaccine virus.
Hence the search for a new and improved type 2 oral vaccine against poliovirus, which retains the good parts of the original but with adjustments to try to avoid 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 reversion” to a disease-causing virus.
Andino and colleagues modified the type 2 vaccine virus in several places. The researchers modified a portion of the virus's genetic instruction book, or genome, so that the virus was less likely to develop a "gatekeeper" change: a critical first step on the road to regaining the ability to cause disease.
Poliovirus can exchange pieces of its genome with related viruses called enteroviruses. Thus, the researchers transferred a series of genetic letters that the virus needs to make more copies of itself near the "gatekeeper" modification. Thus, if the vaccine virus were able to abandon that modification through an exchange, it would also lose this necessary chain of genetic letters and die.
Finally, the team played with an enzyme that RNA viruses, including poliovirus, use to replicate. Andino says the enzyme is sloppy and can introduce many genetic changes. That’s advantageous for viruses, which “continually try to adapt to a new environment,” he says. Andino and his colleagues modified this enzyme in the vaccine virus to introduce fewer errors, "so the virus cannot evolve as fast." The researchers described the enhanced oral polio vaccine in a study conducted at Cell Host & Microbe in May.
The new oral polio vaccine has been shown to be safe and produce an immune response similar to that seen with the original vaccine in infants and children, online researchers reported Dec. 9 in Lancet. The hope is that the changes will slow the evolution of the new vaccine virus so that it can end existing outbreaks without creating new ones.
Vaccine-derived outbreaks are a significant, but overcome, obstacle to polio eradication, Ohuabunwo says, and "science is helping." But the key to ending polio is "very high vaccination coverage." He says obstacles including war, migratory populations, difficult terrain and a lack of acceptance of the vaccine have created inaccessible child bags.
Reaching out to all children requires involving community leaders, providing culturally sensitive information, and figuring out how to meet other community needs, Ohuabunwo says. For example, while working in Nigeria, he and his colleagues progressed with nomadic populations. It meant "sometimes combining the vaccination of your children with the vaccination of your animals." Nomadic cattle would be immunized against brucellosis and anthrax bacterial infections. The protection of animals also protected nomads from these infections, and motivated their cooperation for their children to receive the polio vaccine: "a triumph."
Polio eradication has been a long journey, “but we are getting closer,” Ohuabunwo says. The new oral polio vaccine "is another of the tunnel lights."