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.