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This article was originally published in July 2022 has been updated for inclusion in the Fall 2024 issue of Microcosm.

For most people, (polio) is a threat of the past.

Since the inception of the in 1988, more than 2.5 billion children have been immunized against polio, leading to its elimination from much of the world. Indeed, of the 3 serotypes of wild poliovirus (the causative agent of the disease), only type 1 remains , the 2 countries where polio (i.e., wild poliovirus) is still endemic.

However, cases of polio continue to crop up in across the globe, from the Democratic Republic of the Congo (DRC) to the . In August 2024, Gaza reported its first case of polio in 25 years, prompting an ambitious amid ongoing conflict. What drives these outbreaks—and what can be done to stop them?

Vaccines as Key Tools in the Fight Against Polio

, a serotype of the Enterovirus C species and member of the Picornaviridae family, which infects the gut and throat but can invade the nervous system to cause paralysis. Paralysis occurs in about 1 in every 200 cases, . Children under 5 are the most at-risk for contracting the disease, though the reasons for this are not entirely clear. Given there are no treatments for polio, vaccination is the only tool available for combating the disease. Luckily, vaccination is extremely effective at preventing polio.

There are 2 types of polio vaccines: the and . The IPV contains dead polioviruses and is administered via intramuscular or intradermal injection; it is the only polio vaccine used in the U.S. OPVs, on the other hand, contain live polioviruses and are administered through the mouth. The viruses in OPVs have been mutated to replicate effectively in the gut, thus triggering a robust immune response, but these mutated viruses are 10,000 times less likely to invade the nervous system and cause paralysis.

While IPV does an excellent job of protecting individuals from paralytic disease, it cannot stop community transmission of poliovirus—but OPVs can. When attenuated viruses from OPVs are excreted in a vaccinated person’s stool, they can, in areas with poor sanitation, spread to other people and trigger "passive immunity"—essentially secondhand vaccination.

The ease of administration (all it takes is plopping a few drops of an OPV into a child’s mouth), affordability and ability to stop community spread of polio have made OPVs indispensable to mass immunization and outbreak control campaigns.

Emergence of Circulating Vaccine-Derived Polioviruses

Although OPVs are some of the best weapons available for fighting polio, they have seeded a new set of problems. Recent polio outbreaks in stem from poliovirus strains originally contained in OPVs, called . As cVDPV disperse throughout communities with low polio vaccination rates or waning immunity, they can, in some cases, mutate into a form .

The GPEI’s goal is "to phase-out using OPV[s] and proceed to using just IPV, which has fewer potential risks," said Amy Weiner, Ph.D., a senior program officer at the , which supports polio eradication efforts. This is because the IPV does not contain live virus and thus cannot lead to development of cVDPV. Unfortunately, cVDPV strains "are a major challenge to accomplishing this goal," as they promote community spread of poliovirus, which can only be combated with OPVs, thus perpetuating the cycle.

Of the 3 types of cVDPV, for over 90% of vaccine-associated outbreaks worldwide. The culprits behind polio cases in multiple countries, including the DRC and Nigeria,  have been identified as cVDPV2. A paralytic case of polio in Gaza—and key trigger for the subsequent vaccination campaign—was .

Prior to 2016, children were immunized with a trivalent oral polio vaccine (tOPV), which offered protection against all 3 strains of wild poliovirus. The emergence of cVDPV2 strains, however, prompted the removal of type 2 polio from the tOPV. "This led to reduced immunity to type 2 poliovirus," Weiner noted.

As a result, if cVDPV2 isolates from the environment find their way into an under-immunized community, they can spread more easily. Before 2021, in the event of a cVPDV2-associated outbreak, children were immunized against type 2 poliovirus . Though effective at halting outbreaks, because the vaccine still contained live, attenuated poliovirus, it could "potentially seed more cVDVP2 [strains]," Weiner said. This of unimmunized children contracting paralytic polio.

New Developments: The Novel Oral Polio Vaccine 2

The cVDPV2-seeding potential of mOPV2 prompted development of a new vaccine with fewer risks. The novel oral polio vaccine 2 (nOPV2) contains a modified strain of type 2 poliovirus that is . Weiner highlighted that, compared to the old monovalent vaccine, nOPV2 has a similar safety profile, induces a similar immune response and is unlikely to be shed at a greater rate. Importantly, nOPV2 is more genetically stable (it is to seed new outbreaks), which "was the primary goal for its development."

This isn’t to say the nOPV2 poliovirus does not change—the virus can and does mutate in humans. However, "its evolution follows a different path than the mOPV2 [strain] and, so far, exhibits significantly less neurovirulence," Weiner said. , there is roughly 1 cVDPV2 emergence per 10 million doses of mOPV2 administered; for nOPV2, the rate is 10 times lower, at 1 emergence per 100 million doses. It does happen, however, as evidenced by the appearance of cVDPV2 originating from nOPV2 in 6 African countries between August 2021 and July 2023. Thus, continuing to keep tabs on the emergence of cVDPV2 will be important.

The future of nOPV2 is bright. In 2020, it was authorized for use , which enabled its early, targeted use prior to licensing. During the initial rollout of the vaccine, which began in March 2021, countries had to meet a strict set of criteria to use nOPV2. However, by the end of 2023, nOPV2 received and , allowing for more countries to access the vaccine. To date, over 1 billion doses of nOPV2 have been administered worldwide—it is now the go-to vaccine for preventing or mitigating cVDPV2 outbreaks. Weiner noted that new OPVs targeting poliovirus serotypes 1 and 3 are also in the works, which could be stockpiled in the event of cVDPV1 or cVDPV3 outbreaks.

The Road Ahead

Vaccines alone have never been, and will never be, enough to defeat polio. that couples strong disease surveillance and immunization campaigns with quick responses to outbreaks will be necessary to reduce the burden of polio around the globe. Until outbreaks of both cVDPV and wild poliovirus are under control, polio eradication remains just out of reach.

The history of polio, from its ancient origins to its near-eradication, illustrates the profound impact of scientific advancement, public health initiatives and global collaboration. Check out this next article to learn about the progression of the fight against this debilitating disease.