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A girl receives the oral polio vaccine in Egypt, a candidate country for the introduction of a new vaccine less likely to cause outbreaks.


The polio eradication campaign is faltering. Can a new vaccine help it get back on track?

The Global Polio Eradication Initiative (GPEI) is about to roll out a brand-new vaccine—one that its leaders desperately hope will turn the flagging effort around. If it works as expected, the vaccine just might overcome one of the biggest obstacles to polio eradication: out-of-control outbreaks caused by mutant polio strains derived from the vaccine itself. If not, GPEI will be back to dousing each outbreak with a vaccine that risks starting another, as eradication slips further from sight.

The new vaccine is so urgently needed that the Bill & Melinda Gates Foundation has paid for nearly 200 million doses to be produced by an Indonesian manufacturer “at risk,” even before clinical trials are complete. The World Health Organization (WHO) is ready to grant an emergency use listing, a new approval mechanism never before used for a vaccine, as soon as Indonesia’s regulatory authority gives the product the nod. The first drops could be delivered in several countries by the end of the year.

“All the early signs and data look pretty good,” says Jay Wenger, who leads polio eradication efforts at the Gates Foundation. But he and others concede that clinical trials to date have involved just 1200 people. The vaccine’s full worth won’t be known until it is given to millions of children under close scrutiny.

The problem is Albert Sabin’s oral polio vaccine (OPV), the workhorse of the eradication program, now in its fourth decade. OPV is cheap, effective, and easy to use, needing just two drops on a child’s tongue. It is made from a living virus, attenuated, or weakened, so it can’t paralyze but can still replicate in the gut. This means children shed the vaccine virus in their stool for a few weeks after they receive it, spreading it to others who are not vaccinated and protecting them, too. (The killed, injected vaccine adopted by most rich countries protects against paralysis but does not block circulation.) Massive OPV immunization campaigns have driven the wild polio virus almost to extinction; it is now holed up in just Pakistan and Afghanistan.

In places where immunization rates are low, however, OPV can continue to pass among susceptible children for several weeks, mutating as it goes until it has regained its ability to paralyze and spread. This problem is especially acute for the type 2 virus, one of three polio serotypes. Scientists realized long ago that this meant they would eventually have to stop using OPV. But OPV is still the only vaccine that can quash outbreaks in the poor, hot settings where the virus thrives.

GPEI’s answer was to phase OPV out one serotype at a time after each was eradicated in the wild. Type 2, last seen in 1999, would be the first to go. Over 2 weeks in April 2016, all countries stopped using trivalent OPV and replaced it with bivalent OPV, with the type 2 component removed—a trial run for the eventual cessation of all OPV. The plan was to snuff out the few type 2 outbreaks that would inevitably emerge from the last use of trivalent vaccine with a limited, emergency stockpile of a vaccine effective against just type 2, known as monovalent OPV2 (mOPV2).

The move worked in most places, but mOPV2 spawned new outbreaks in some others. Twenty-three countries, most of them in Africa, are now battling vaccine-derived outbreaks, and the vaccine virus is paralyzing more children than the wild type. The problem is rapidly getting worse, in part because children born after the switch no longer have gut immunity—which is key in polio—to type 2. So far this year, more than 600 vaccine-derived cases have been recorded, five times as many as by this point in 2019.

The new vaccine, in the works since 2011 and known as novel OPV2 (nOPV2), is an improved version of Sabin’s vaccine, painstakingly engineered to be more genetically stable by a global consortium of dozens of researchers at institutions including the United Kingdom’s National Institute for Biological Standards and Control; the University of California, San Francisco; the U.S. Centers for Disease Control and Prevention (CDC); and the U.S. Food and Drug Administration.

The Sabin vaccine was created in the 1940s and ’50s by passaging the virus through animal cells until scientists found a suitably weakened form. They now know a few mutations at one end of the viral genome are key to weakening it. To “tighten” or stabilize these Sabin mutations, scientists introduced 18 nucleotide changes at the so-called 5’ end of the viral genome. One change, explains the Gates Foundation’s Ananda Bandyopadhyay, who co-chairs the nOPV2 working group at GPEI, was to block a single point mutation that seems to be the “gatekeeper,” preceding other events leading to virulence. Another route back to neurovirulence comes when the Sabin virus recombines with related viruses and loses the modified 5’ end altogether. The team reduced the chance of this happening by disabling a key element in the middle of the genome, inserting a new one near the stabilized 5’ end, and making other tweaks.

Data from preclinical research and phase I and II studies in adults, children, and infants in Belgium and Panama are “very, very reassuring,” Bandyopadhyay says: The vaccine appears to be as safe and effective as the Sabin vaccine, and so far, extensive sequencing analyses have turned up no evidence of dangerous reversion. Now, the “million-dollar question” is exactly how stable the vaccine will be when used in a much larger population, says WHO’s Simona Zipursky, who co-chairs the nOPV2 working group.

Wenger hopes it will be hundreds of times more stable. “But [even] a 10-fold increase, which is not much, would be a huge change,” he says. “It doesn’t have to be absolutely perfect to be useful. It could be enough to let the program catch up.”

Hopefully, we will stop lighting new fires. That is the hope.

Mark Pallansch, U.S. Centers for Disease Control and Prevention

“I think it is indeed a much, much better vaccine than monovalent OPV2,” says WHO’s Ondrej Mach, GPEI’s team lead for R&D. “But we simply have to be 100% sure.” There is a theoretical possibility that the changes aimed at preventing recombination might not work—“a very low probability, high-consequence event” that could undermine faith in the eradication effort, he says. That’s why the rollout will be done with “an abundance of caution,” Zipursky says, “so if anything unexpected happens, we will be able to identify it and respond to it quickly.”

Because the new vaccine will be approved for emergency use only, countries must have an ongoing outbreak. But to meet WHO’s27 strict criteria for the 3-month “initial-use” period, they cannot have used mOPV2 in the same area for the past 12 weeks, because that would make it harder to assess how the vaccine is doing. The problem is that countries don’t have the luxury of waiting until the new vaccine is ready; when a new outbreak occurs, they must act immediately with mOPV2. This has resulted in a changing cast of candidate countries as GPEI has waited for WHO’s emergency use approval, originally expected this summer.

Countries must also approve emergency use of the vaccine and be able to monitor safety and efficacy, and they have to be able to transport any type 2 isolate to a reference lab for sequencing—fast—to determine whether it arose from the novel vaccine or past use of the monovalent vaccine. Liberia, the Republic of Congo, Sudan, and Egypt are now on the list, says Michel Zaffran, who is stepping down as head of GPEI at the end of the year.

If safety continues to look good and nOPV2 seems to be more stable, “those would be positive signals to roll it out in a bigger way,” says John Vertefeuille, who leads polio efforts at CDC. GPEI expects to ramp up production to 600 million doses a year.

As high as hopes are for the new vaccine, the eradication program still faces perilous times. Cases of both wild and vaccine-derived virus were already shooting up in 2019, and the COVID-19 pandemic has only made things worse, as GPEI paused campaigns from March to July. Some countries have been slow to resume, giving the virus free rein to circulate and spark new outbreaks.

And even if nOPV2 works as planned, stopping outbreaks will be just as hard as it is with mOPV2, says Mark Pallansch, a polio expert at CDC. It depends on reaching enough children to boost population immunity high enough so the virus can no longer circulate—and countries with ongoing outbreaks have, by definition, been falling short. But even if the new vaccine doesn’t quash all vaccine-derived outbreaks, Pallansch says, “Hopefully, we will stop lighting new fires. That is the hope.”

*Update, 15 November, 1:55 p.m.: WHO announced it had issued the emergency use listing for nOPV2 on 13 November.

*Correction, 12 November, 8:15 a.m.: An earlier version of this story said the oral polio vaccine is causing outbreaks. In fact, the outbreaks are caused by mutant polio strains derived from the oral vaccine.