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A New Polio Vaccine Could Battle Its Resurgence

TRecent polio outbreaks have been a shocker. It was in 1979 that polio was officially declared eradicated in the U.S.—an early step in a multi-generational effort to wipe out the disease around the world. The New York State Department of Health reported a case of Polio in a Rockland County man on July 21st. Since then, there has been poliovirus in New York City and Orange County wastewater. The virus was found in London’s wastewater in February and Jerusalem in the same month.

The three cases, though seemingly isolated, point to a troubling trend—one that goes against more than three decades of progress in eradicating the disease. In 1988, polio was endemic in 125 countries and led to the death or paralysis of 350,000 people—mostly children—each year, according to the World Health Organization (WHO). But thanks to a massive vaccination push by the WHO, Rotary International, UNICEF, the U.S. Centers for Disease Control and Prevention (CDC), and more, polio is now endemic in just two countries—Afghanistan and Pakistan—which have seen only 18 cases between them so far this year.

Polio, however, is creeping back, and health officials are now on the alert for what Paul Andino-Pavlovsky, a professor of microbiology and immunology at the University of California, San Francisco, calls a “silent epidemic” of the disease around the world. “This is just the tip of the iceberg,” he warns.

Adds Yvonne Moldanado, a professor of global health and infectious disease at Stanford University School of Medicine, “The case we saw [in New York]This was not a common occurrence, but it is a warning sign that there could be more cases of paralytic disease. We do run the risk of developing more cases of paralytic disease.”

Unfortunately, polio continues to stalk us. The good news is that just in the past year, a new vaccine has been added to the arsenal of existing polio vaccines—one that, properly deployed, could halt a new global outbreak of polio before it can get started. No matter what, the reappearance of the disease has raised a host of challenges—all of which need to be met if we’re to keep polio contained.

What’s behind the current outbreak?

Multiple factors have played a role in the return of polio—not the least of which is complacency, especially in the U.S. and other developed countries. When a majority of people alive have never encountered a case of a given disease, it’s easy to put it out of mind. “People don’t remember polio, they don’t see it,” says Ian Lipkin, professor of epidemiology at Columbia University’s Mailman School of Public Health. “There’s something about our species that just allows us to forget about the importance of these things.”

That can lead to a slow erosion in vaccine compliance—something that the numbers bear out in the U.S. Nationwide, 92.6% of children are fully vaccinated against polio by age 2, according to the CDC. Broadly speaking, that’s an encouraging figure, but vaccination rates vary state to state and even county to county. Oklahoma has a polio vaccine rate of 79.5% while South Carolina’s is at 80.3%. Alarmingly, 37.3% of Rockland County’s zip codes have polio cases.

In the return of the disease, the COVID-19 epidemic has played an important role. “During the COVID era, families didn’t see their doctors or pediatricians as frequently as they normally would,” says Dr. William Schaffner, professor of infectious diseases at Vanderbilt University School of Medicine in Nashville, Tenn. “That has resulted in children falling behind in their routine vaccination schedules.”

Moldanado claims that there has been a very small drop in the polio vaccine rates for children, and only a 1% decrease since the outbreak of the pandemic. Infectious diseases can be very important. Even a 1% difference in polio vaccination rates could make a big difference. “It translates to tens of thousands of kids who aren’t completely vaccinated,” Moldanado says, “and those children are at risk for diseases that really shouldn’t exist in well-resourced countries.”

Continue reading: Polio Is Back. Here’s How to Keep Yourself Safe

The vaccine paradox

The irony of polio’s comeback is that the very vaccination campaign the CDC estimates has prevented 16 million cases of paralysis and 1.5 million deaths since 1988 is also partly responsible for the new resurgence. There are two types of polio vaccines. The first, known as the inactivated polio vaccine (IPV)—administered by injection—uses a killed virus to familiarize the body with the disease and prime it to recognize and attack a live virus if it ever encounters it. The other, known as the oral polio vaccine (OPV)—administered by mouth—uses an attenuated, or weakened, virus that can do the same job of priming the immune system, without actually causing the disease. The advantage of the OPV is that it’s easier and cheaper to administer, which is why it’s used in global eradication campaigns. There is a chance that the weaker vaccine could revert back to the original virus strain in rare cases. That can potentially lead to the disease in the person who received the vaccine, and even if it doesn’t, the reinvigorated virus is shed in feces, entering wastewater and potentially infecting other people. For that reason, the U.S. switched to the IPV exclusively in 2000—even though cases of viral reversion were exceedingly rare.

“The crude estimate was one in 3 million doses of oral vaccine administered would lead to a case of polio in the U.S. before 2000,” Schaffner says. “It’s rare, but it’s not inconsequential.”

Indeed it’s not. The virus responsible for the cases of polio in New York City and Jerusalem, as well as the one found in London’s wastewater, was identified by genetic sequencing. According to the Global Polio Eradication Institute (GPEI), cVDPV has been responsible for 535 additional cases of polio this year in 18 countries.

But the IPV has its problems too—in addition to its comparative difficulty of administration. The OPV, since it’s taken orally, establishes what’s known as gut immunity. If the recipient of the vaccine does not become a virus-infected person, the vaccine will prevent any viral replication and therefore no virus from being shed into the stool. While the IPV will protect you from contracting polio in the future, it doesn’t prevent your intestinal virus replication.

Andino-Pavlovsky is of the opinion that sampling water in areas where IPVs are used will likely reveal some vaccine-derived poliovirus. IPV recipients have replicated and shed the virus, putting unvaccinated persons at risk. “In Europe, in America, in Australia—every place where people are using the inactivated vaccine—it is likely,” he says.

A new vaccine

Although there are some drawbacks with both vaccines it is better to get vaccinated than not, as all vaccine recipients have protection against contracting symptoms of polio. However, the OPV & IPV are in tension. One produces vaccine-derived viral and the other contributes to its spread. For that reason, the WHO and other global health organizations call for an eventual switchover to the IPV exclusively—a move that would mean there would be no vaccine-derived virus to be picked up and shed at all.

“We need to stop giving the live virus so it stops circulating,” says Moldanado.

That, however, is not practical at the moment—not while there are still millions of babies and children who need vaccines in the developing world, where the IPV remains too pricey and skilled vaccinators who can administer injections are in far shorter supply than field workers who require little special training to administer drops to the mouth. As a stopgap, the WHO, the Bill and Melinda Gates Foundation, and the U.K.’s National Institute for Biological Standards and Control have come together to develop a new oral vaccine that is far more stable than previous versions, reducing the likelihood of the attenuated virus used in the drops ever reverting to its virulent state.

Andino-Pavlovsky is part of the team responsible for the design of the vaccine. It works by targeting the area on the viral genome which causes reversions to virulence. To be considered dangerous, this part of the existing OPVs must go through a single mutation.

“What we basically did was modify this sequence,” he says, “so a single point mutation cannot cause reversion; a virus now has to go through four or five different changes before acquiring a more virulent phenotype. Basically, it’s a numbers game.” As Andino-Pavlovsky earlier described it to the journal Nature, “It’s like putting the virus in an evolutionary cage.

This vaccine, which contains the caged virus, was released at 2021’s end. More than 180 million doses of it have been distributed in 13 countries, Andino Pavlovsky claims. “The new vaccine is as effective as the previous one in generating immunity,” he says, “[and is] able to stop the silent epidemic.”

The goal, ultimately, is to drive polio over the cliff to extinction—as smallpox was in 1980—with a slow phase-out of all OPV, universal use of IPV, and the eradication of any form of poliovirus circulating anywhere in the world. This is why the current return to polio is so alarming. We will be haunted by an old curse until it ends.

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Send an email to Jeffrey Kluger at jeffrey.kluger@time.com.

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