Despite conducting some of the most successful international vaccination campaigns in history, the poliovirus continues to circulate worldwide, posing a threat of neurological damage and paralysis to unvaccinated individuals.
While wild poliovirus strains have been largely eradicated, the oral polio vaccine (OPV) widely used in developing countries can generate new strains. OPV utilizes attenuated live polioviruses that can occasionally mutate back to a virulent form, leading to outbreaks in countries considered polio-free.
In a recent study, researchers from the University of California, San Francisco, and the National Institute for Biological Standards and Control (NIBSC) in the United Kingdom developed two novel oral polio vaccines (nOPV): nOPV1 and nOPV3, to support the World Health Organization’s (WHO) recent efforts towards the final eradication of poliovirus. Two years ago, WHO began using their first developed nOPV, known as nOPV2. These nOPVs mark the first batch of new polio vaccines in 50 years.
Similar to the first nOPV, these two latest nOPVs described in the new study are genetically engineered, attenuated forms of the poliovirus, designed to reduce the risk of the virus mutating into its dangerous form. The development of these nOPVs was led by Dr. Raul Andino, Professor of Microbiology and Immunology at the University of California, San Francisco, and Dr. Andrew Macadam, a virologist at NIBSC.
Andino said, “Due to differences in vaccination coverage within and between countries, the poliovirus has persisted into the 21st century, sometimes with tragic consequences. We have designed these new vaccines based on lessons learned from years of fighting polio and believe they will contribute to its permanent elimination.”
The fight against polio continues to develop
Polio is insidious—it is often asymptomatic, but approximately one in every hundred children infected with the virus will suffer severe disabilities, paralysis, or even death. It spreads through fecal-oral transmission, making it particularly problematic in areas with poor sanitation. In the first half of the 20th century, polio frequently caused outbreaks in the United States, triggering a race to develop a vaccine.
The first effective polio vaccines emerged in the 1950s, sparking large-scale immunization campaigns targeting everyone, with a focus on children. The inactivated polio vaccine (IPV), made from inactivated poliovirus, is administered through injection, while the oral polio vaccine (OPV), made from attenuated poliovirus, is given in the form of sugar cubes or drops. Today, IPV is the preferred vaccine in countries with robust healthcare systems, while OPV is a cheaper and more manageable option.
In populations where everyone receives immunization in early life, whether they receive IPV or OPV is not crucial, although these vaccines have different roles in the environment. Individuals vaccinated with IPV can still be infected with any circulating poliovirus without getting sick, but they can silently transmit the virus to unvaccinated individuals. People vaccinated with OPV cannot spread the circulating poliovirus in this manner, but they can shed the attenuated vaccine virus and transmit it to the unvaccinated. If this attenuated poliovirus undergoes mutation, it can again cause paralytic polio.
In populations of unvaccinated children—whether due to vaccine refusal, natural disasters, or conflicts—vaccine-derived polioviruses can spread widely, causing severe illness in a small number of unfortunate individuals.
While wild poliovirus has been recently detected in Afghanistan and Pakistan, vaccine-derived polioviruses have been found in distant countries such as Syria, the Democratic Republic of the Congo, and the United States. In fact, in recent years, there have been more cases of polio caused by vaccine-derived viruses than by wild viruses, highlighting the urgency to combat this new source of poliovirus.
In 2017, Andino and his colleagues discovered how OPV can revert to its harmful form: a single mutation can restore the virus’s ability to migrate from the human gut to the nervous system. Within a few years, they artificially introduced three mutations, greatly reducing the possibility of genetic reversion, and packaged them into a new vaccine.
This vaccine, known as nOPV2, was included in the World Health Organization’s Emergency Use Listing in 2020, becoming the first-ever vaccine to receive such recognition, and it was rapidly manufactured and distributed.
Andino said, “Over 600 million doses have been shipped to 28 countries, and in 10 of them, it has halted the ongoing outbreaks of vaccine-derived polio. It gives us confidence that it is actually working as anticipated.”
Covers all the foundations of polio eradication
Despite the effectiveness of nOPV2, it provides protection against only one of the three strains of poliovirus, and recently, cases of polio have emerged in heavily vaccinated areas such as Israel and some regions in the United States where parents refuse to have their children vaccinated.
Even in places where there are no reported cases of polio, the virus is still detected in wastewater in major cities. Today, polio cases may have decreased by 99% compared to 30 years ago, but eradicating the remaining 1% has proven to be challenging. “As long as there is any place with poliovirus and a gap in vaccination, it will rebound,” said Andino.
This new research takes the solutions developed by these authors for nOPV2—three specific mutations that typically prevent vaccine-derived polioviruses from becoming dangerous over time—and applies them to the other two strains of OPV. The resulting vaccines, nOPV1 and nOPV3, effectively prevent polio in animal models. All three vaccines are much safer than the original OPV, which occasionally caused paralysis in recipients, although this occurrence is rare.
Both of these new vaccines are currently undergoing clinical trials to ensure their efficacy and safety, preventing the dangerous reversion of the virus in the human body. Andino hopes they will be incorporated into a bivalent or trivalent combination with nOPV2. Future generations of children will be protected as well, remaining free from the impact of polio throughout their lives, and perhaps one day the world will experience decades without detecting any cases of polio.