No Room for Complacency as Vaccine-Derived Viruses Can Lead to Polio’s Return

A little girl receiving an oral polio vaccine in India in 2011. Credit: cdcglobal/Flickr, CC BY 2.0

A little girl receiving an oral polio vaccine in India in 2011. Credit: cdcglobal/Flickr, CC BY 2.0

As the world inches closer toward polio eradication, researchers caution against complacency. Vaccine-derived polio viruses excreted by people with low immunity could lead to polio re-emergence in the post-eradication era, especially as there is currently no effective strategy to treat these patients, they report.

The $16.5 billion, ambitious global polio eradication programme is nearing its goal. Of the three polio types, wild 2 and 3 types appear to have been eradicated, and type 1 is mostly confined to a region of Afghanistan and Pakistan.

There has been no polio case caused by circulating wild type 2 poliovirus since 1999, no case caused by wild type 3 since November 2012 and the last case of type 1 in Africa was in August 2014, leaving some areas of Afghanistan and Pakistan as the main remaining reservoirs.

This means that any type 2 or 3 case would be vaccine derived polio virus (VDPV). All type 2 polio cases since 1999, except an isolated incident of 10 cases linked to a wild laboratory reference strain in India, are due to vaccine-related poliovirus strains in either recipients, their immediate contacts or after the vaccine virus regained the ability to transmit and circulate freely, a report in the journal PLOS Pathogens says.

“Vaccine-derived poliovirus (VDPV) strains can be generated and transmitted from person to person in populations with low immunity and have been associated with a number of polio outbreaks around the world,” it continues. The circulating VDPVs (cVDPV) “behave very similarly to wild polioviruses and should therefore be eliminated by the same immunisation methods.”

A quiet threat

A team of researchers led by Javier Martin, from the division of virology at the National Institute of Biological Standards and Control, Hertfordshire, UK, followed up a particularly interesting case of a person with low humoral immunity, who has been excreting the type 2 polio virus in his stools for some 28 years. He is apparently the longest excreter of the VDPV – of 73 such cases of persons with low immunity excreting VDPVs on Martin’s list.

The researchers referred to VDPVs from low-immunity individuals as iVDPV to distinguish them from vaccine derived viruses from normal, healthy vaccinated persons, and tested them in both the laboratory and mice for their genetic characteristics and ability to cause infection. This is because the “risks posed by iVDPV strains and the prevalence of such cases globally are unknown”, and it is difficult to assess their possible future impact on global polio eradication drive, the researchers reported.

The UK team studied 186 stool samples of the person, obtained between 1995 and 2015. They found 10,000 infectious virus particles per gram, which was comparable to virus levels in samples from healthy vaccinated persons and paralysis cases caused by the wild polio virus or the vaccine, Martin explained to The Wire.

The latest virus isolate, from a stool sample collected in March 2015, showed a 17.7% accumulation of genetic changes in the virus’s genetic material. “These changes result in loss of the attenuation properties of the vaccine virus,” Martin said.

Also, the antiviral treatment did not work and the virus growth was not affected.

Overall, the results show that the viruses are excreted in high numbers, are extremely virulent and have acquired genetic changes. This “raises questions about how the population may best be protected from them, particularly in the light of possible changes in vaccine production which are being encouraged to increase capability and reduce costs,” the report in PLOS Pathogens reads. Such ‘chronic excretions’ could jeopardise the polio eradication programme.

These viruses also “could potentially cause poliomyelitis in susceptible people, so it is very important to maintain high levels of vaccine coverage and surveillance activities,” Martin said.

Sharp surveillance

Two types of polio vaccines are already in use. One is the killed Salk vaccine (developed by Jonas Salk), which consists of chemically inactivated wild poliovirus (all three types), and is given as an injection. The Salk vaccine predominantly induces systemic antibodies that protect against disease by preventing its spread from the gut to the nervous system. However, the Salk vaccine does not induce strong mucosal immunity, and so poliovirus can replicate freely in the intestines of even vaccinated individuals and the infection can then be spread to unvaccinated contacts.

The second is the Sabin vaccine (developed by Albert Sabin), which is a live, attenuated vaccine, containing weakened vaccine strains of all three polio virus types. It is given orally, replicates in the intestines of vaccinees, induces both mucosal and systemic immunity, and protects against infection of the intestine by ingested virulent poliovirus. But it can also revert to a virulent form, and there are documented cases of outbreaks caused by circulating reverted Sabin poliovirus from areas from which the natural virus had been previously eradicated. The Sabin vaccine has been used to eradicate the polio virus from most of the planet.

Renowned polio vaccine expert T. Jacob John, a retired professor at the Christian Medical College (CMC), Vellore, and member of the National Technical Advisory Group on Immunisation (NTAGI) said India too has had eight instances of iVDPV from 2009 to 2013.

As healthcare has advanced, B cell related immunodeficient persons live long with reasonably good health, John explained. Some of them would have taken the oral polio vaccine (OPV) in childhood while a few would be chronically infected.

“There may be others about whom we may know nothing until some crisis happens. That could be a person developing polio due to the chronic iVDPV, which can happen after global polio eradication,” John added.  Another eventuality is the spread of iVDPV to non-immune persons, leading to circulation and then polio – of one or more cases. “We have to be aware and vigilant – and we are.”

Martin said that surveillance “is particularly important at this end stage of the global polio eradication initiative” to minimise the risk of polio coming back.

Chances of outbreaks

According to him, research results would help design optimal strategies for the polio-eradication endgame, including improved surveillance to quickly detect and characterise poliovirus from clinical and environmental samples, and vaccination schemes and antiviral treatments to complete eradication and minimise the risk of a polio comeback.

John also said that Sabin viruses in OPV is a double edged tool. Immunodeficient persons have this peculiar phenomenon of chronic infection, which does not happen with wild polioviruses. “So it is a biological curiosity with unexplained reasons.”

Second, Sabin viruses rarely cause paralytic polio, which is indistinguishable from wild virus polio except that the virus is vaccine Sabin.

Finally, vaccine viruses can spread and lose their attenuation (their weakened state) and become wild-like, even causing polio outbreaks. John estimates that there may be some 400-500 polio cases annually due to Sabin-origin viruses – more than cases caused by wild viruses, thanks to eradication efforts.

“The benefit to risk ratio that was acceptable in the past is no longer acceptable now,” and a switch to an injectable polio vaccine (IPV) is a must, advises John. India and all other oral polio vaccine (OPV) using countries will introduce IPV in 2015/16 and, thereafter, the trivalent OPV vaccine that works against all three types will be replaced with the bivalent OPV containing only types 1 and 3.