British and US scientists have collaborated to “super-engineer” polio vaccines to prevent them from mutating into a dangerous form that can cause outbreaks and paralysis, with results of the first-stage human trials being “very promising”.
Polio can spread into the nervous system, causing paralysis, but fortunately, cases have fallen by more than 99% since the late 1980s: about 2m people who would have been paralysed can walk, thanks to vaccines.
The original or “wild” poliovirus is now contained to small pockets in Afghanistan and Pakistan, and the oral vaccines play a pivotal role in the attempt to rid the world of polio.
“The issue, however, is they’re genetically unstable,” Dr Andrew Macadam, from the UK’s National Institute for Biological Standards and Control, told BBC News.
It takes only one mutation to turn the safe polio vaccine back into a virus that can move out of a child’s stomach, invade their nervous system and cause paralysis.
And if those viruses spread from an immunised child – through their contaminated faeces – there is a risk of infecting the unvaccinated and triggering an outbreak.
There are now more cases of “vaccine-derived polio” than of the wild poliovirus and the polio detected in London’s sewers last year was connected to the oral vaccine.
So the researchers have genetically altered the weakened virus even further to make it much harder for it to start causing paralysis again.
“By genetically modifying this part of the virus, we could modify this region so it couldn’t revert, and this, I think has been remarkably successful,” said Macadam.
Professor Raul Andino, from the University of California San Francisco, said he was “super-proud” of the scientific effort showing the vaccine was “50 to 100 times more stable”.
In March 2021, the World Health Organisation made the researchers’ vaccine against type two polio available for emergency use. Since then, it has been used more than 650m times.
Now, in the journal Nature, the researchers have detailed the creation of stable vaccines against polio types one and three.
The first-stage human trials of the upgraded vaccines have already been conducted, and the data, say the researchers, are still being analysed but are “very promising”.
The trio represents the first new polio vaccines in 50 years.
“I don’t think there’s any question that they’re helpful… the new vaccines address the instability question, but not the coverage issue,” Macadam said.
‘Impressive science’
Tackling the last 1% of polio cases has proven stubborn. The original goal was to completely eradicate polio by the year 2000, but delivering vaccines to some of the poorest and most conflict-ridden parts of the world has been a challenge.
Joseph Swan, from the WHO and the Global Polio Eradication Initiative, said more stable vaccines were a “significant part” of the plan for a polio-free world.
But, he said: “Simply having these new and better tools will not get us over the finish line: vaccination, not just vaccines, is what will end polio.”
Study details
Genetic stabilisation of attenuated oral vaccines against poliovirus types 1 and 3
Ming Te Yeh, Matthew Smith, Sarah Carlyle, Jennifer L. Konopka-Anstadt, Cara C. Burns,
John Konz, Raul Andino & Andrew Macadam
Published in Nature on 14 June 2023
Abstract
Vaccination with Sabin, a live attenuated oral polio vaccine (OPV), results in robust intestinal and humoral immunity and has been key to controlling poliomyelitis. As with any RNA virus, OPV evolves rapidly to lose attenuating determinants critical to the reacquisition of virulence resulting in vaccine-derived, virulent poliovirus variants. Circulation of these variants within under-immunised populations leads to further evolution of circulating, vaccine-derived poliovirus with higher transmission capacity, representing a significant risk of polio re-emergence. A new type 2 OPV (nOPV2), with promising clinical data on genetic stability and immunogenicity, recently received authorisation from the World Health Organization for use in response to circulating, vaccine-derived poliovirus outbreaks. Here we report the development of two additional live attenuated vaccine candidates against type 1 and 3 polioviruses. The candidates were generated by replacing the capsid coding region of nOPV2 with that from Sabin 1 or 3. These chimeric viruses show growth phenotypes similar to nOPV2 and immunogenicity comparable to their parental Sabin strains, but are more attenuated. Our experiments in mice and deep sequencing analysis confirmed that the candidates remain attenuated and preserve all the documented nOPV2 characteristics concerning genetic stability following accelerated virus evolution. Importantly, these vaccine candidates are highly immunogenic in mice as monovalent and multivalent formulations and may contribute to poliovirus eradication.
BBC News article – Super-engineered vaccines created to help end polio (Open access)
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