Jessica Crothers, M.D., assistant professor of pathology and laboratory medicine, works in a Vaccine Testing Center lab in UVM's Stafford Building. (Photo: Bailey Beltramo)

A Rutland, Vermont physician described the first outbreak of polio in the United States in 1894. Then, in 1980, it was declared eradicated in the United States. Now, 42 years later, the fear of polio has returned to the region.

In the past several months, cases of polio have been reported in New York, the United Kingdom, and Israel, underscoring the need for safer and more effective vaccines. Over the past nearly two years, University of Vermont Vaccine Testing Center researchers have been conducting trials on two experimental polio vaccines poised to help accomplish global eradication.

Like SARS-CoV2, the virus that causes COVID-19, poliovirus is an RNA virus. It infects the nervous system, which is why infected persons experience paralysis. But polio is eradicable, says Jessica Crothers, M.D., assistant professor of pathology and laboratory medicine and lead investigator on the polio vaccine trials, “because it is a human reservoir disease, meaning that it does not naturally infect animals other than humans.”

In fact, thanks to vaccines, polio remains endemic in only two countries – Pakistan and Afghanistan – where wild type (not vaccine-derived) poliovirus infections are still occurring.

The reason for the recent cases in previously certified polio-free regions, Crothers explains, is due to asymptomatic transmission of the virus from travelers to regions where either wild type or vaccine-derived virus is currently circulating back into their home environments, where it eventually can infect unvaccinated or immunosuppressed populations.

The oral polio vaccine (also known as the Sabin vaccine) is a live attenuated virus that produces a mild infection in the gastrointestinal (GI) tract and creates immunity without causing disease. But because the virus is in the GI tract, it replicates there and is shed via stool into the environment. The virus can mutate overtime – as we’ve seen with SARS-CoV2 variants – and become stronger, eventually making it capable of causing disease in unvaccinated or immunosuppressed people susceptible to infection.

“The majority of poliomyelitis cases worldwide – 99 percent – are now caused by circulating vaccine-derived virus,” Crothers says.

The first of the two trials, launched at UVM in 2021, was a first-in-human Phase I study of a novel Oral Polio Vaccine for poliovirus serotypes 1 and 3 (nOPV1,3). Performed in collaboration with PATH, a nonprofit organization focused on health equity and innovation, the trial is funded by the Bill and Melinda Gates Foundation. The oral polio vaccine in this trial has been genetically modified to prevent it from regaining its ability to cause disease while being shed in the environment. A version of this vaccine for poliovirus serotype 2 has already been approved for emergency use authorization in Europe.

The nOPV1,3 trial enrollment recently ended, with roughly 80 participants, and is in the final stages of data collection. The second trial, which launched this fall, is looking for study volunteers to test a modified version of the inactivated polio vaccine (Salk vaccine) delivered via an injection in the arm. This trial includes use of a mucosal adjuvant – added components designed to improve mucosal immunity in the gut, so that vaccinated people do not shed the virus in their stool and risk transmitting it to others. This study is being done in collaboration with the World Health Organization and their Global Polio Eradication Initiative.

“Urgency has returned to the fight against polio,” says Crothers, who is hopeful that polio will follow the course of another human reservoir disease – smallpox. “Global vaccination campaigns were successful in eradicating smallpox in 1979, so that children now do not need to be vaccinated against it,” she says, eager for these safer, more effective vaccines to be able to bring the world to the home stretch of what will hopefully be the next successful eradication story.

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The Vaccine Testing Center is currently recruiting healthy volunteers, age 18-45, for the inactivated polio vaccine trial, which is an outpatient study. Information about volunteering in the trial is available on the web, via email at uvmvtc@uvm.edu, or phone at 802-656-0013.