A young man was diagnosed this summer in New York City with paralysis caused by a virus that is part of a live polio vaccine. A little earlier, in the spring, several cases of unvaccinated people being infected by vaccine-derived poliovirus were detected in Jerusalem. The virus from live vaccines is regularly found in wastewater samples around the world. Molecular biologist and science journalist Irina Yakutenko explains what’s going on, how dangerous such vaccines are, and whether the world faces new outbreaks of a disease that seemingly has been almost completely eradicated.
Victims of hygiene
The great success of live vaccines
Potential man-caused epidemic
Victims of hygiene
Polio is one of the worst mass diseases, killing thousands of children each year and leaving hundreds of thousands partially or completely paralyzed. Polio symptoms have been known since ancient Egypt: for example, a pylon dating back to the 18th dynasty (1570-1342 BC) has a carved image of a priest with a very typical lesion on the lower part of his right leg and on the sole of his right foot. Pharaoh Siptah’s mummy, dating back to the late 19th dynasty (1342-1197 BC), shows that his left leg was paralyzed and very typically crooked from suffering polio.
But despite such a long contact with humans, poliovirus did not cause major outbreaks, much less epidemics, for a long time. A slow increase in the number of polio infections began at the very end of the eighteenth century and led to a real disaster in the early twentieth. Until the launch of the global vaccine campaign to eradicate the virus, the annual number of symptomatic cases reached 350,000, and it was mostly young children who fell sick. The reason for the sudden lethal activity of the virus was... hygiene. Until the end of the XVIII century mankind did not particularly value cleanliness - and hundreds of thousands of child deaths due to various intestinal infections were the consequence. The spread of soap and, in principle, the habit of washing hands dramatically reduced the severity of the problem - but at the same time, more and more children began coming down with a severe form of polio.
With the spread of soap, more and more children began coming down with a severe form of polio
While previously infants became exposed to the virus transmitted through the fecal-orally route when they ate mother's milk, since mothers began washing their hands before picking up their babies, the first encounter with poliovirus often occurred after weaning, e.g. without the protection of the mother's antibodies from her milk. Maternal antibodies against the poliovirus prevented the pathogen from multiplying too vigorously while the infant's body produced its own defenses. Without the protection of maternal antibodies, the virus easily overpowered the child's immune system.
There was no specific treatment for the symptomatic form of the disease or ways to somehow reduce the risk of developing paralysis and its severity - and there still isn't. If the virus reaches the central nervous system and begins to multiply in the motor neurons of the spinal cord or brain, or in the nerve cells that transmit signals from the brain to the muscles, the inevitable death of the neurons leads to the failure of the limbs and/or respiratory muscles. These changes are often irreversible, and while patients with milder forms of paralytic polio ended up with crutches, iron leg braces or wheelchairs, the most severely affected patients were saved by using so-called iron lungs, metal chambers with a pump that pumped air in and out of the chamber, forcing the chest to rise and fall passively. Children and adults who contracted polio and whose respiratory muscles became paralyzed were forced to spend weeks, years – or even their entire lives - in those chambers.
Although polio can be contracted throughout the year, most of the powerful outbreaks occurred in late summer or early fall. Parents tried to protect their children by keeping them out of swimming pools, movie theaters, and playgrounds, but those restrictions did little to protect them. At the height of the epidemic in 1952, 21,000 cases of paralysis - mostly in children - were reported in the United States alone. Thanks to the media, including television, even people not directly affected by polio were aware of what was happening.
The great success of live vaccines
At the time, scientists already knew how of the existence of viruses and bacteria, knew how to deal with them and how to develop the simplest vaccines, containing either killed or attenuated viruses. Many groups were working on polio vaccines, and the initial versions of live vaccines appeared in the mid-1930s. However, they did not meet even minimum standards of safety and reliability, so the first truly mass-produced vaccine did not appear until 1952. It was an inactivated (that is, containing killed virus) vaccine developed by a group led by the American virologist Jonas Salk. Tests on hundreds of thousands of children showed that the drug afforded effective protection against severe polio and slightly less effective, but still satisfactory, protection against infection.
A global vaccination campaign against polio was launched in 1955, and almost immediately the number of cases fell by orders of magnitude: in 1953, 35,000 infections were recorded in the U.S., 5,600 in 1957, and only 161 in 1961. The apparent success was overshadowed by an extremely unpleasant story in 1955, when 40,000 children were infected with polio after receiving a wrong inactivated vaccine produced by a pharmaceutical company called Cutter. Ten of those infected died. The publicity and the ensuing investigation had a major impact on the vaccine industry, forcing regulators to significantly tighten the testing standard for vaccines.
But the reputation of inactivated polio vaccines took a hit anyway, and when in 1961 a live, weakened vaccine, created under the direction of Albert Sabin, a Polish-born American scientist, and containing variants of all three known serotypes, became widely available, it quickly supplanted the Salk vaccine. An additional advantage of the live vaccine over the inactivated vaccine was its ability to generate powerful immunity in the mucous membranes of the digestive tract: that’s where both wild and attenuated viruses from the vaccines multiply. The inactivated vaccine (IPV, inactivated polio vaccine), which is injected into the muscle in the upper arm, is excellent at stimulating systemic immunity but hardly “reaches” the partially autonomous mucosal immunity. The live vaccine is dripped into children's mouths, given to drink in a spoonful of syrup, or to eat on a lump of sugar, so it goes straight into the digestive tract where the viruses from the vaccine begin to multiply.
Those vaccinated with the Sabin vaccine (OPV, oral poliovirus vaccine) were not only protected against a severe course: strong immunity in the intestinal mucosa prevented the virus from multiplying if the vaccinated person encountered it. And so, unlike those vaccinated with IPV, such people did not become spreaders of the pathogenic virus, but rather a dead end that interrupted the chain of virus transmission. Moreover, the newly vaccinated worked as sources of supplemental immunization: for a few weeks after receiving a dose of OPV, while the weakened vaccine viruses were actively multiplying in their intestines, they could infect unimmunized people, affording them protection.
All these advantages, plus the fact that no syringes were required, made OPV the vaccine of first choice in the vast majority of countries for a long time. But almost immediately, a serious flaw was discovered in the live vaccine: on rare occasions, weakened viruses from the vaccine could mutate, regaining their pathogenicity. In most of the cases it did not happen in the vaccinated person's body: in order to accumulate the necessary number of changes the virus had to travel for some time through the bodies of unvaccinated, IPV-inoculated (with lower efficiency) or immunocompromised people (in such people, in extremely rare cases, paralysis can also be caused by the vaccine-derived virus, which keeps reproducing in their bodies for very long periods). As a result, the virus which again learned to case the disease infected unvaccinated individuals and some of them developed a severe form. With OPV, the average rate of paralysis was about 3 cases per million doses. Compared to the 5,000 cases of paralysis of varying severity per million people prior to the launch of the vaccination campaign, this was an acceptable risk.
On rare occasions, weakened viruses from the vaccine mutated and infected the unvaccinated
But as the wild-type polio virus disappeared - serotype 2 was completely eradicated in 2015, serotype 3 in 2019 - the comparative number of vaccine-associated polio cases began to exceed those caused by the wild-type virus, with pockets of the latter remaining only in Afghanistan and Pakistan. To eliminate the risks of disease caused by modified viruses from live vaccines, developed countries decided to phase them out entirely and switch to OPV only. Since the early 2000s, much of the wealthy nations have switched to inactivated vaccine only. But most of the world still uses a combination setup (first IPV, then OPV), and although serotype 2 of poliovirus, which caused up to 94% of all vaccine-associated polio cases, was almost completely excluded from live vaccines in 2016, cases of illness and paralysis due to vaccine-derived virus infection are still being detected. Since 2017, there have been 396 cases of polio caused by the wild-type virus and more than 2,600 cases of disease associated with the vaccine-derived virus.
Poor countries can't give up using live poliovirus vaccine, primarily for financial and logistical reasons. OPV is much cheaper than IPV, and it can be administered to children not only by health workers. In addition, during the transition period, countries may need stockpiles of live vaccines containing only one serotype of poliovirus in order to quench possible outbreaks of vaccine-associated poliomyelitis. Theoretically, the WHO could facilitate a universal switch to IPV, but, as the Covid pandemic showed, the organization’s ability to influence government policies is very limited.
Potential man-caused epidemic
As a result, OPV-vaccinated, IPV-vaccinated, and unvaccinated people are now living next to each other. This combination, given the growing number of unimmunized children and the ability to travel to the other side of the planet in a few hours, creates a perfect environment for the spread of a modified virus from live vaccines. A rough scenario looks like this: a child who has recently received a dose of live vaccine and is therefore actively excreting attenuated polioviruses in her feces flies from a country where OPV is being actively used to, say, the United States, where this vaccine has not been used since 2000. In other words, all young Americans who have already received only IPV - or no vaccine at all - can serve as passive spreaders of vaccine-derived viruses. Transmitted from person to person, such viruses can acquire the very changes they need to regain pathogenicity. When such a virus enters the body of an unvaccinated person, it can cause a symptomatic disease, clinically indistinguishable from poliomyelitis caused by a wild-type virus.
And that is exactly what appears to have happened in New York City, where a young unvaccinated man developed paralysis in the Rockland County area. It is home to a compact, orthodox Jewish community, with a polio vaccination rate of about 37%. The virus that caused the paralysis belongs to serotype 2 of vaccine-derived viruses - but it has acquired about 10 mutations along the way from vaccine to sick person. Sewage tests in New York City revealed the exact same virus, and a comparison of its genome against the genomes of polioviruses found earlier this year in London and Jerusalem sewage showed that the pathogens were related to one another. The New York patient had not traveled to an area where he might have encountered poliovirus shortly before his symptoms appeared, which means it can be assumed he was infected by some of the type 2 vaccine-derived virus transmitters – either IPV-vaccinated or unvaccinated - who left a viral trail in the sewage. It is not known who and when brought the virus to New York, but it is clear that this person was somehow part of the “silent” chains of infections linked to London and Jerusalem.
And this is not the first time such chains have manifested themselves. In March 2022, an unvaccinated three-year-old girl in Jerusalem developed paralysis from polio, and sample tests showed it was caused by a virus derived from Sabin's type 3 vaccine. It differed from the original virus by 17 mutations. Varieties of this virus had previously been found in the sewage of Jerusalem and Bethlehem, which means that in this case we are not dealing with accidental infection but rather with long-term circulation of, and changes to, the original vaccine-derived virus. By April 15, medics found six more children (and later two more) infected with the same poliovirus. Five were unvaccinated and one child had been partially vaccinated.
It can be assumed that the actual spread of circulating polioviruses from live vaccines is much wider. Testing wastewater for pathogens is labor-intensive and is not a routine procedure in many regions. Sporadic measurements have found polioviruses derived from live vaccines in London (although wastewater there is routinely tested) and New York, and even two different variants have been found in Israel. If we study sewage systematically, we can probably learn a lot about other regions as well.
The latent circulation of vaccine-associated polioviruses poses a danger primarily to the non-immune. After vaccinations have rid humanity of a host of deadly pathogens that used to claim hundreds of thousands of children's lives, vaccine skepticism has started to increase systematically. An additional dramatic dip in vaccination occurred because of coronavirus restrictions, and today the number of children vulnerable to viruses and bacteria that have not been definitively eradicated is particularly high. In response to cases of poliovirus-induced paralysis, emergency vaccination campaigns were launched in Israel and London to vaccinate all non-immune children - but vaccination was not compulsory, and parents were only encouraged to vaccinate their children.
But to solve the problem globally, OPV must be discontinued globally, and all unvaccinated children must be vaccinated with IPV. Without this, “runaway” vaccine strains will continue to circulate, periodically regaining pathogenicity. Theoretically, this scenario looks feasible, but in practice the likelihood of centralized replacement of OPV with IPV in poor countries is close to zero – one might recall the complete failure of the Covax campaign to supply coronavirus vaccines to the countries in need. In Africa, for example, only 21.1% of the population was fully vaccinated against coronavirus by early July 2022, while in many nations of the continent vaccination rate did not even reach 10 percent.
Another scenario is to replace serotype 2 of poliovirus in live vaccines (it mutates more frequently than the others and causes the most cases of vaccine-associated poliomyelitis) with a more genetically stable one. The OPV containing this altered strain was approved for emergency use in 2020, but it has not yet seen mass distribution. Perhaps cases of paralysis induced by vaccine-derived poliovirus in developed countries will spur efforts to introduce such OPV. If the situation remains as it is, we should expect a wider spread of the virus derived from live vaccines and new cases of disease, paralysis, and death.