2018, which was three times the number of cases due to wild viruses not derived from the vaccine. As the number of children who have no immunity to type 2 poliovirus increases, this number may rise.
Health officials are campaigning to eliminate all oral vaccines and rely on injected vaccines containing killed virus. However, this plan imposes logistic and financial burdens on developing countries. Meanwhile, oral type 2 vaccines are needed to stop any outbreaks of type 2 polio. And health officials have not yet figured out how to make sure unvaccinated children don’t get polio from mutated viruses shed by vaccinated people.
Ensuring virulence can’t be restored
But what if researchers created a vaccine from a weakened live virus that’s unlikely revert to virulence? That’s one of the strategies that several research groups are working on now.
As part of this effort, scientists have now mapped out in detail the steps that allow the PV2 vaccine strain to regain virulence.
Just three simple genetic mutations, each of which alone has a small effect, when combined, dramatically increase the virulence of the PV2 strain in mice in the lab. And, all three are found in the viruses shed by recent vaccine recipients.
Virulence can also be reestablished in the intestine if the genetic material of the PV2 strain recombines with that of another virus. The second virus can be the weakened PV1 or PV3 from the vaccine, or a related virus such as coxsackie, a common virus in children.
Designing the virus for the vaccine
Having discovered exactly how the type 2 vaccine virus regains virulence, scientists figured out ways that these specific genetic changes could be prevented. Using the tools of molecular biology, they made four important changes to the PV2 genome that should stop it from regaining virulence.
Part of the virus’s RNA genome has to fold up into a lollipop-like shape in order for proteins to be made. This structure is disrupted in the weakened vaccine strain, but a single mutation in the virulent strain allows it to reassemble. So that can’t happen, the scientists changed the genetic sequence of the RNA in a way that no single nucleotide change would let the RNA fold into the stable lollipop structure again.
Second, they changed the genetic sequence of the enzyme that copies the RNA to make it more accurate. That way fewer genetic mutations would occur in the vaccine recipient’s intestine.
Third, another change to the same enzyme reduced the chance that the virus could pick up genes by recombining with other viruses in the recipient.
And, fourth, they rearranged the virus’s genes so that replacing certain regions of its own RNA with genetic information from a wild virus, such as coxsackie, would be lethal for it.
Researchers have produced two candidate PV2 viruses that grew well in experimental cells, were not virulent in a mouse model and were genetically stable. A phase 1 clinical trial of vaccines made from these viruses showed that they were well tolerated, produced an immune response and had reduced (but not zero) reversion to virulence compared to the original oral vaccine for PV2.
These and other new, rationally designed viruses have the potential to provide good protection from polio with a reduced risk of creating new outbreaks due to circulating vaccine-derived polio virus.
[ Like what you’ve read? Want more? Sign up for The Conversation’s daily newsletter. ]