A unique clinical trial to bolster polio eradication efforts

June 4, 2019 by PATH

Construction of the container village, known as Poliopolis at the University of Antwerp.

Construction of the container village, known as Poliopolis at the University of Antwerp. Photo: University of Antwerp

How PATH, its partners, and a container village at the University of Antwerp are striving toward a polio-free world.

If you visited the University of Antwerp in the summer of 2017, you’d be unlikely to miss an unusual site: two long rectangular boxes, like shipping containers with windows, spanning the length of several parking spaces.

Most unusual, though, is what the boxes contained: two sequential groups of 15 volunteers who agreed to remain within its walls for 28 days, while they participated in the first-in-human clinical trial of two novel oral polio vaccine candidates against type 2 poliovirus (nOPV2). The first group received one candidate; the second group received the other.

It’s the first study on new strains of oral polio vaccines to get this far in more than half a century.

The results, published in the Lancet, provided key safety and immunogenicity data, which, support the advancement of both nOPV2 candidates into further testing. If these trials are successful, an nOPV2 could be submitted for World Health Organization (WHO) Emergency Use Listing in 2020 and, if regulators and policymakers agree, deployed for use soon after to bolster eradication efforts.

The rules of containment

The University of Antwerp, a partner in the nOPV2 project coordinated by PATH, put this special infrastructure in place to satisfy recently developed WHO guidelines for the containment of type 2 polioviruses.

Given global progress against this disease, activities involving all forms of live poliovirus type 2, including attenuated (weakened) strains, must exercise extreme caution to prevent its release into the environment. The innovative research for new and better vaccines, however, is crucial, as we will need type 2 vaccines stockpiled to protect against outbreaks for many years to come.

Though it was called a “container village,” it functioned more like an island to minimize the risk of transmission until the behavior of these novel strains in humans was better understood.

Photo: University of Antwerp

Volunteers stayed quarantined for 28 days to test the safety of a novel vaccine that holds potential to bolster eradication efforts. Photo: University of Antwerp

Oral polio vaccines are created with an attenuated version of the live virus. Because the vaccine is given orally, this weakened virus passes through and replicates in the intestinal tract to induce immunity, and is subsequently “shed” (a euphemism for the vaccine strain exiting the body in fecal matter).

It’s extremely rare, but occasionally in under vaccinated populations, the shed vaccine virus can be transmitted from person-to-person, eventually returning to its virulent form (termed circulating vaccine-derived poliovirus, or cVDPV). These cVDPV strains are especially concerning in areas where many people are not vaccinated and can potentially cause polio disease.

The contained facility, called Poliopolis, had an unconnected, free-standing plumbing system that enabled researchers to decontaminate waste to prevent any shed vaccine virus from reaching the environment.

Poliopolis had common areas, including a gym, and private rooms for each participant. Photo: University of Antwerp.

Poliopolis had common areas, including a gym, and private rooms for each participant. Photo: University of Antwerp.

“Novel” solutions to current vaccine limitations

The staggering advances we’ve made against polio would not have been possible without the current oral polio vaccine (OPV). It’s brought us tantalizingly close to the dream of making polio the second disease (after smallpox) to be eradicated.

High OPV coverage continues to be the best way for communities to protect themselves against cVDPVs. Yet because OPV is used in low-resource settings, where immunization coverage can be low, cVDPV outbreaks are especially tenacious in the areas where they can cause the most harm and are an obstacle to eradication efforts.

nOPV could hold the key to snuff out cVDPVs. They are “novel,” or new, because the early research suggests that the approaches used to attenuate the nOPV strains make them more “genetically stable” than current OPV (meaning, less likely to mutate back into its dangerous form). It suggests that nOPV could have all the protective benefits of current OPV and hold a smaller chance of seeding cVDPV outbreaks. Such an advantage could allow for better control of outbreaks.

Phase 2 trials with larger sample sizes are underway. This time, thanks to the encouraging results from the Phase 1 trial, the volunteers can circulate on and off site as they please.

One day, with continued innovation and investment, the same will not be said for polio.

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