The Vaccine Loophole in Polio Eradication

In 1988, the World Health Assembly announced a very ambitious goal: Polio was to be vanquished by the year 2000. It was a reach, sure, but feasible. Although highly infectious, polioviruses affect only people, and don’t hide out in wild animals; with two extraordinarily effective vaccines in regular use, they should be possible to snuff out. Thanks to a global inoculation campaign, infections had, for years, been going down, down, down.

But 2000 came and went, as did a second deadline, in 2005, and a third, in 2012, and so on. The world will almost certainly miss an upcoming target at the end of 2023 too. In theory, eradication is still in sight: The virus remains endemic in just two countries—Pakistan and Afghanistan—and two of the three types of wild poliovirus that once troubled humanity are gone. And yet, polio cases are creeping up in several countries that had eliminated them, including the United Kingdom, Israel, and the United States. Earlier this year, New York detected America’s first paralytic polio case in nearly a decade; last week, the governor declared a state of emergency over a fast-ballooning outbreak.

This is the cruel logic of viruses: Give them enough time—leave enough hosts for them to infect—and they will eventually find a way to spread again. “You have to stop transmission everywhere, all at the same time,” says Kimberly Thompson, a health economist and the president of the nonprofit Kid Risk. Which means eradication will demand a near-perfect syncing of vaccine supply, access, equity, political will, public enthusiasm, and more. To beat the virus, population immunity must outlast it.

Right now, though, the world’s immunological shield is too porous to stop polio’s spread. At the center of the new epidemics are vaccine-derived polioviruses that have begun to paralyze unimmunized people in places where immunity is low—a snag in the eradication campaign that also happens to be tightly linked to one of its most essential tools. Vaccine performance has always depended on both technology and human behavior. But in this case especially, because of the nature of the foe at hand, those twin pillars must line up as precisely as possible or risk a further backslide into a dangerous past.

In the grand plan for eradication, our two primary polio vaccines were always meant to complement each other. One, an ultra-effective oral formulation, is powerful and long-lasting enough to quash wild-poliovirus transmission—the perfect “workhorse” for a global vaccination campaign, says Adam Lauring, an evolutionary virologist at the University of Michigan. The other, a supersafe injectable, sweeps in after its colleague has halted outbreaks one country at a time, maintaining a high level of immunity in post-elimination nations while the rest of the world catches up.

For decades, the shot, chaser approach found remarkable success. In the 1980s, wild poliovirus struck an estimated 300,000 to 400,000 people each year; by 2021, the numbers had plummeted to single digits. But recently, as vaccine coverage in various countries has stalled or slipped, the loopholes in this vaccination tactic have begun to show themselves and grow.

The oral polio vaccine (OPV), delivered as drops in the mouth, is one of the most effective inoculations in the world’s roster. It contains weakened forms of polioviruses that have been altered away from their paralysis-causing forms but still mimic a wild infection so well that they can stop people from spreading wild pathogens for years, even decades. In the weeks after people receive the vaccine, they can also pass the weakened virus to others in the community, helping protect them too. And OPV’s transportability, low price point, and ease of administration make it a “gold standard for outbreak interruption,” says Ananda Bandyopadhyay, the deputy director for the polio team at the Bill & Melinda Gates Foundation. Since its mid-20th-century debut, OPV has helped dozens of countries—including the U.S.—eliminate the virus. Those nations were then able to phase out OPV and switch to inoculating people with the injected vaccine.

But OPV’s most potent superpower is also its greatest weakness. Given enough time and opportunity to spread and reproduce, the neutered virus within the vaccine can regain the ability to invade the nervous system and cause paralysis in unvaccinated or immunocompromised people (or in very, very rare cases, the vaccine recipient themselves). Just a small handful of genetic modifications—three or fewer—can spark a reversion, and the mutants, which are “better at replicating” than their kin, can take over fast, says Raul Andino, a virologist at UC San Francisco. In recent years, a few thousand cases of vaccine-derived polio have been detected around the world, far outstripping the toll of wild viruses; dozens of countries, the U.S. now among them, are battling such outbreaks, and the numbers seem to be only going up. Vaccine-derived polio is still a true rarity: Billions of oral vaccines have been delivered since the global campaign began. But it underscores “the real problem” with OPV, Lauring told me. “You’re fighting fire with fire.”

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The injected polio vaccine, or IPV, which contains only chemically inactivated versions of the virus, carries none of that risk. To purge all polio cases, “you have to stop using oral polio vaccine,” Thompson told me, and transition the entire globe to IPV. (Post-eradication, countries would need to keep IPV in their routine immunization schedule for at least 10 years, experts have said.) But the injected vaccine has a different drawback. Although the shot can very effectively stave off paralysis, IPV doesn’t elicit the kind of immunity that stops people from getting infected with polioviruses and then passing them on. In places that rely on injected vaccines, “even immune individuals can participate in transmission,” Thompson told me. Which opens up a vulnerability when too many people have skipped both types of vaccines: Paralyzing polioviruses erupt out of communities where the oral vaccine is still in use—then can spread in undervaccinated areas. It might be tempting to blame OPV for our troubles. But that’s not the main threat, Bandyopadhyay told me. “It’s the lack of adequate vaccination.”

As things stand, the goal in the endemic countries of Pakistan and Afghanistan remains achieving sufficiently high vaccine coverage, Bandyopadhyay said. But many of the communities in these nations are rural or nomadic, and tough to reach even with convenient drop-in-the-mouth vaccines. Civil and political unrest, misinformation, natural disasters, and most recently, the COVID pandemic have raised additional hurdles. So have intermittent bans on house-to-house vaccination in Afghanistan, says John Vertefeuille, the chief of the polio-eradication branch at the CDC. Cases of wild polio have experienced a recent jump in Pakistan, and have also been imported into the non-endemic countries of Malawi and Mozambique.

But the toll of those outbreaks—all featuring type 1 polio—currently pales in comparison with those featuring vaccine-derived type 2. The last case of wild type 2 polio was detected in 1999, but that version of the virus has persisted in its modified form in oral polio vaccines. And when it reverts to its dangerous form, it gains particularly infectious oomph, allowing it to spread unchecked wherever immunity is low. Some 30 countries around the world are battling outbreaks of poliovirus whose origin can be traced back to the oral inoculations; vaccine-derived type 2 is what’s been circulating in Jerusalem, London, and New York, where it ultimately paralyzed an unvaccinated young man. The extent to which the virus is churning in other parts of the country isn’t fully known; routine immunization has dropped since the COVID pandemic’s start, and the U.S. hasn’t regularly surveyed its wastewater for the pathogen.

The success of these vaccine-derived viruses is largely the result of our own hubris—of a failure, experts told me, to sync the world’s efforts. In 2016, 17 years after the last wild type-2 case had been seen, officials decided to pivot to a new version of OPV that would protect against just types 1 and 3, a sort of trial run for the eventual obsolescence of OPV. But the move may have been premature. The switch wasn’t coordinated enough; in too many pockets of the world, type-2 polio, from the three-part oral vaccine, was still moseying about. The result was disastrous. “We opened up an immunity gap,” Thompson told me. Into it, fast-mutating vaccine-derived type-2 viruses spilled, surging onto a global landscape populated with growing numbers of children who lacked protection against it.

A new oral vaccine, listed for emergency use by the WHO in 2020, could help get the global campaign back on track. The fresh formulation, developed in part by Andino and his colleagues, still relies on the immunity-boosting powers of weakened, replicating polioviruses. But the pathogens within have had their genetic blueprints further tweaked. “We mucked around” with the structure of poliovirus, Andino told me, and figured out a way to make a modified version of type 2 that’s far stabler. It’s much less likely to mutate away from its domesticated, non-paralyzing state, or swap genes with related viruses that could grant the same gifts.

Technologically, the new oral vaccine, nicknamed nOPV2, seems to be as close to a slam dunk as immunizations can get. “To me, it’s just super cool,” Lauring told me. “You keep all the good things about OPV but mitigate this evolutionary risk.” In the year and a half since the vaccine’s world premiere, some 450 million doses of nOPV2 have found their way into children in 22 countries—and a whopping zero cases of vaccine-derived paralysis have followed.

But nOPV2 is “not a silver bullet,” Andino said. The vaccine covers just one of the three poliovirus types, which means it can’t yet fully replace the original oral recipe. (Trials for type-1 and -3 versions are ongoing, and even after those recipes are ready for prime time, researchers will have to confirm that the vaccine still works as expected when the three recipes are mixed.) The vaccine’s precise clinical costs are also still a shade unclear. nOPV2 is a safer oral polio vaccine, but it’s still an oral polio vaccine, chock-full of active viral particles. “You can think of it as more attenuated,” Thompson said. “But I don’t think anybody expects that it won’t have any potential to evolve.” And nOPV2’s existence doesn’t change the fact that the world will still have to undergo a total, coordinated switch to IPV before eradication is won.

As has been the case with COVID vaccines, and so many others, the primary problem isn’t the technology at all—but how humans have deployed it, or failed to. “Vaccine sitting in a vial, no matter how genetically stable and how effective it is, that’s not going to solve the problem of the outbreaks,” Bandyopadhyay said. “It’s really vaccination and getting to that last child in that last community.”

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If dwindling vaccination trends don’t reverse, even our current vaccination strategies could require a rough reboot. In 2013, health officials in Israel—which had, for years prior, run a successful IPV-only campaign for its children—detected wild type-1 virus, imported from abroad, in the country’s sewage, and decided to roll out another round of oral vaccines to kids under 10. Within a few weeks, nearly 80 percent of the targeted population had gotten a dose. Even “polio-free countries are not polio-risk-free,” Bandyopadhyay told me. The situation in New York is different, in part because type-1 polio causes paralysis more often than type-2 does. But should circumstances grow more dire—should substantial outbreaks start elsewhere in the country, should the nation fail to bring IPV coverage back to properly protective levels—America, too, “may have to consider adding OPV as a supplement,” says Purvi Parikh, an immunologist and a physician at NYU, “especially in rural areas” where emergency injected-vaccine campaigns may be tough. Such an approach would be a pretty extreme move, and a “very big political undertaking,” Thompson said, requiring a pivot back to a vaccine that was phased out of use decades ago. And even then, there’s no guarantee that Americans would take the offered oral drops.

The CDC, for now, is not eager for such a change. Noting that most people in the U.S. are vaccinated against polio, Katherina Grusich, an agency spokesperson, told me that the CDC has no plans to add OPV or nOPV to the American regimen. “We are a long way from reaching for that,” she said.

But this week, the U.S. joined the WHO’s list of about 30 nations with circulating vaccine-derived-poliovirus outbreaks. The country could have avoided this unfortunate honor had it kept shot uptake more uniformly high. It’s true, as Grusich pointed out, that more than 90 percent of young American children have received IPV. But they are not distributed evenly, which opens up vulnerabilities for the virus to exploit. Here, the U.S., in a sense, had one job: maintain its polio-free status while the rest of the world joined in. That it did not is an admonition, and a reminder of how unmerciful the virus can be. Polio, a fast mutator, preys on human negligence; the vaccines that guard against it contain both a form of protection and a catch that reinforces how risky treating these tools as a discretionary measure can be.