Years in the making: the World Health Organization prequalifies type 2 novel oral polio vaccine

January 11, 2024 by Hope Randall

How PATH’s product-to-impact expertise helped guide the novel oral polio vaccine to approval.

A decade in the making, novel oral polio vaccine against type 2 poliovirus (nOPV2) could help the world finally reach eradication. Photo: World Health Organization.

Type 2 novel oral polio vaccine (nOPV2) could help the world finally reach eradication. Photo: World Health Organization.

More than a decade ago, a group of researchers began advancing a groundbreaking new polio vaccine called nOPV2. By the time it came to PATH’s doorstep in 2015, it was ready for clinical testing.

In late 2020, nOPV2 became the first vaccine to receive an Emergency Use Listing, just ahead of the COVID-19 vaccine. Three years and nearly one billion doses later, nOPV2 achieved WHO prequalification, a key milestone to ensure broad, long-term access.

Here are a few key contributions PATH made along the way.

Genetic stability for a safer vaccine

Sabin oral polio vaccines (OPVs) have brought the world to the brink of eradication, but pockets of low immunization coverage leave the door open for a threat to arise—circulating vaccine-derived poliovirus.

Though it is a rare phenomenon, the weakened poliovirus strain used in OPVs can revert to a virulent form after being shed from the body. This is most frequently seen with the strain used in the traditional type 2 oral polio vaccine (OPV2). The world is so close to eradication, that these rare, circulating, type 2 vaccine-derived cases now outnumber wild polio cases—and as a result—pose a challenge to eradicating the disease.

The primary way to tamp down the threat of vaccine-derived cases has been to use OPVs to vaccinate as many people as possible in the community. Researchers created nOPV2 for outbreak response with the aim of having a more genetically stable vaccine that is less likely to revert to a virulent form in the first place.

When nOPV2 was ready for clinical testing, PATH became the coordinating body of the research effort—serving as a critical mechanism for data-sharing among partners, giving technical input into the clinical trial study design, and compiling, collating, and analyzing data—lots of data.

We also provided technical input into a unique Phase 1 trial that involved quarantining participants, who lived in a temporary, self-contained facility called Poliopolis for 28 days. This was before COVID-19, and it felt novel at the time.

A novel testing strategy

Polio vaccine safety tests are standard practice but advancing nOPV2 required an even deeper analysis than usual: we needed to conclusively demonstrate that nOPV2’s weakened vaccine virus was more genetically stable (less likely to revert to a virulent state) than the weakened virus used in OPV2.

To do that, we used a lab test that models human disease to compare the levels of virulence (potential to cause disease) between vaccine virus samples shed from participants of nOPV2 and historic OPV2 studies. To complement and cross-reference those findings, we used a process called next-generation sequencing. This process creates a map of the shed vaccine virus genome, allowing us to see if it has changed in ways that would affect its virulence.

We looked for specific changes in the virus that are known, or have the potential, to contribute to a reverted virulent state in OPV2 shed virus. We paid close attention to the behavior of these genomic regions in our analysis of nOPV2 shed virus to detect any potentially problematic changes.

In applying these unique methods to one Phase 1 trial and two Phase 2 trials, we demonstrated that nOPV2 is less likely to revert to a virulent form than Sabin OPV2. Real-world use of the vaccine reinforced these findings.

Facilitating efficient vaccine approval

In November 2020, during an undoubtedly heavy year for global health, PATH and partners celebrated a bright spot when nOPV2 became the first vaccine to receive an Emergency Use Listing by the World Health Organization (WHO)—just before COVID-19 vaccines began gaining the same approvals and brought this technical regulatory procedure to major news headlines.

In our work alongside partners to pursue an Emergency Use Listing for nOPV2, PATH facilitated data-sharing among partners, a prerequisite to submitting the needed information to WHO review committees; used our regulatory experience to coordinate partners’ engagement with WHO review processes; and ensured the sequencing of activities maximized efficiencies in the rolling data submissions.

In parallel to EUL approval, PATH sponsored a Phase 3 trial in The Gambia to collect the data required by WHO for prequalification and helped integrate the evidence into the application. nOPV2 received WHO prequalification in December 2023, ensuring the vaccine will be broadly available for years to come.

Our work on nOPV is not over yet: we’re also advancing research and development efforts for nOPVs against polio types 1 and 3.

The need for innovation will continue until the world is finally free from the threat of polio. Vaccines bring us closer—and we’re working to ensure that these novel vaccines bring us closer, faster.

PATH is the convener of the nOPV2 research consortium.
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