In 2002, a new strain of the coronavirus family appeared in in Southeast Asia that causes severe acute respiratory syndrome, or SARS. The disease quickly spread worldwide, with a 10% mortality level among those infected.
In a study published today in the journal PLoS Pathogens, scientists from the CNB-CSIC explain how they were able to modify the SARS virus to develop a safe vaccine that is 100% effective against the disease.
The first candidate vaccine was developed already in 2014 in the CNB laboratory led by researcher Luis Enjuanes. This prototype consisted of live SARS virus attenuated by removal of its envelope gene E. The scientists showed that this vaccine provided complete protection against reinfection by the virulent virus in mouse models.
"However, we later detected a safety problem with this candidate vaccine, as viruses that replicated in cells or in mice accumulated changes and reverted to the virulent state. This meant that our vaccine was not safe, "explains Enjuanes.
The reason for this reversion was that, when the E gene was removed, a protein motif very important for virus replication was also eliminated and the virus evolved to recover it.
To prevent this from happening, instead of completely eliminating the E gene, the scientists removed small fragments that do not destroy the virus’s essential motif. They were thus able to attenuate the virus in a way that it cannot recover its virulence.
In addition, to increase vaccine safety, small deletions were made in a second gene far away from the first. This makes it very unlikely that the virus will be able to recover its pathogenicity.
"By understanding the molecular mechanisms that confer virus pathogenicity and assessing genetic stability in vivo, we have obtained a very promising SARS vaccine that, in addition to being effective, is safe" concludes Enjuanes.
- Jimenez-Guardeño JM, Regla-Nava JA, Nieto-Torres JL, DeDiego ML, Castaño-Rodriguez C, Fernandez-Delgado R, et al. (2015) Identification of the Mechanisms Causing Reversion to Virulence in an Attenuated SARS-CoV for the Design of a Genetically Stable Vaccine.PLoS Pathog 11(10): e1005215. doi:10.1371/journal.ppat.1005215