An oral vaccine able to replace today's oral polio vaccines that target type 2 poliovirus is urgently needed to address an outbreak of vaccine-derived polio, suggests a new study published March 19 in Science.
There were three natural or "wild" types of poliovirus until type 2 was eradicated in 2015. Although wild type 2 infections haven't been observed for more than 20 years, in 2000 researchers identified mutant viruses derived from the type 2 polio vaccine (OPV2) as the source of some rare cases of paralytic polio.
Despite the withdrawal of OPV2 in 2016, this statistical modelling study demonstrates that the after-effects of its administration continue to contribute to the highest number of vaccine-derived type 2 poliovirus outbreaks and transmission rates to date.
Children across the world who have never been immunized against type 2 poliovirus remain poorly equipped to fight the mutated virus, given that the only available vaccine that prevents transmission has been discontinued and the new oral vaccine is not yet ready.
"This study has illustrated that the world is currently facing an increasing spread of type 2 circulating vaccine-derived poliovirus outbreaks across parts of Africa, Southeast Asia and the Middle East, posing a major challenge to the eradication effort," said lead author Grace Macklin, a Ph.D. student at London School of Hygiene and Tropical Medicine and consultant for the World Health Organization.
Polio, along with Ebola and COVID-19, has been classified Public Health Emergencies of International Concern by the WHO.
"While it is difficult to draw comparisons with coronavirus at this time, this prevalence of infectious disease shows a need for strong health systems across the world to rapidly detect outbreaks and respond to them effectively," said Macklin.
Consider the path of type 2 poliovirus. During the six to eight-week interval after inoculation by OPV2, when the body continues to excrete the virus to build up immunity, the weakened virus from the vaccine can on occasion undergo mutations into a harmful, paralytic form. The vaccine-derived virus could mutate even further once transmitted to an under-immunized community.
Increased incidence of vaccine-induced poliovirus led to withdrawal of OPV2 in April 2016. The Global Polio Eradication Initiative instituted a global switch from trivalent oral polio vaccine, which protects against all three polio strains, to bivalent oral polio vaccine, which protects against type 1 and type 3. This is commonly referred to as "the Switch."
After the Switch, circulation of type 2 polioviruses was expected to disappear. Instead, cases of vaccine-derived poliovirus continue to be reported across several continents, posing a threat to unvaccinated children born after the Switch, who lack any immunity against type 2 poliovirus. Vaccination with OPV2 is currently the only available method to induce immunity and prevent transmission among these children, but further use of OPV2 risks seeding more of the mutated poliovirus.
"These circulating vaccine-derived polioviruses can spread just like wild-type poliovirus: all countries run the risk of being infected until the viruses have been fully eliminated everywhere," said Macklin.
In their new study, Macklin and her colleagues showed the probability of new vaccine-derived poliovirus outbreaks and person-to-person transmission is increasing over time.
They ran statistical models on data from acute polio paralysis cases obtained through the Global Polio Laboratory Network (GPLN).
According to their analysis, the vaccine-derived virus emerged between May 2016 and November 2019. Between these dates, GPLN had detected 859 strains of the vaccine-derived virus across 26 countries — of which 65.5% were most likely seeded after the Switch, the researchers found. They identified 62 post-Switch vaccine-derived poliovirus events and 41 outbreaks in various African and Asian countries.
Shortly after the first mutant polio outbreaks after the Switch, monovalent OPV2 vaccine, protecting against only type 2 poliovirus, was rolled out again in quantities of more than 300 million doses. This outbreak response caused 27 of the total 41 outbreaks between 2016 and 2019.
Based on these findings, Macklin and fellow researchers argue that other types of poliovirus derived from vaccines hold potential to mutate into virulent forms. Thus, complete removal of OPV vaccines — targeting types 1, 2 and 3 — is essential to halt the spread of paralytic polio.
New tools are urgently needed, said Macklin. A new OPV2 vaccine is currently in phase II clinical trials and under review by the WHO Emergency Use Listing — the same process that could eventually review existing data on safety and efficacy of a potential coronavirus vaccine. The updated polio vaccine will be more genetically stable, with a substantially lower risk of seeding vaccine-derived poliovirus. But in case the vaccine takes too long or lacks efficacy, back-up strategies are critical, noted Macklin.
"It is important to remember that, as with all other vaccines, the impact of novel OPV2 will depend on the implementation of high-quality vaccination campaigns," said Macklin. "Increased political commitment is essential to stop the spread of vaccine-derived poliovirus: the situation is a Public Health Emergency of International Concern and has to be treated as such."