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Years in the making: new polio vaccine approved for emergency use

April 26, 2021 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.

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.

Ten years 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, the data were already promising, but even the best health innovations face obstacles on their way to the people and communities who need them.

Fortunately, navigating these obstacles is what PATH does best. Today, with PATH support, nOPV2 has gained Emergency Use Authorization from the World Health Organization, a key milestone before beginning rollout in regions at high risk of polio outbreaks.

Genetic stability for a safer vaccine

Current 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.

Until now, 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. But researchers created nOPV2 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 demonstrate that nOPV2’s weakened vaccine virus was more genetically stable (less likely to revert to a virulent state) than the weakened virus currently used in OPV2.

To do that, we used a modified test to compare the levels of virulence (ability 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 current OPV2.

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 approval 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.

But our work on nOPV2 didn’t end with the Emergency Use Listing approval.

Long-term accessibility of nOPV2 is contingent upon eventual WHO prequalification of the vaccine. To that end, PATH is sponsoring a Phase 3 trial in The Gambia to collect the data required by WHO for long-term accessibility of nOPV2 and will lend our expertise to the prequalification application process. 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 hope these novel vaccines bring us closer, faster.

PATH is the convener of the nOPV2 research consortium.
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