Live-attenuated strains of improved genetic stability

The current live-attenuated vaccine strains of poliovirus are genetically unstable and capable of rapid evolution in human hosts, resulting in reversion to neurovirulence and, occasionally, disease. They can also be shed by recipients for a considerable time after vaccination. This raises questions about how and when to stop vaccination after wild-type viruses have been eliminated. Persistence of vaccine revertant viruses in the population would present a risk to new cohorts of unvaccinated children and threaten the success of the eradication programme. A number of Sabin vaccine strain derivatives have been described that are, in theory, genetically more stable than the present vaccines and therefore less likely to revert to virulence. The approaches used in their derivation are outlined here and data presented for two strains showing a significant improvement in genetic stability. These strains were designed according to our understanding of the molecular basis of attenuation and incorporate changes in the sequence of an RNA structural domain that plays a key role in attenuation. They may also be less transmissible than the current type 3 vaccine strain and are potentially useful in the strategically difficult final stages of poliomyelitis eradication.