Friday, February 3, 2017

New Options for Safer, Thermostable Polio Vaccine

Scientists at the University of Leeds have come up with a poliovirus vaccine that has the immunogenicity of a live attenuated virus without the risks associated with live virus.

The idea for using virus-like particles (VLPs) for polio vaccination has existed for a while, but was impractical until now. Essentially, the VLP is the capsid (protein coat) of the polio virus, without the genetic material inside. This is great, because the capsid stimulates an immune response when given to a human, but since there is no genetic material, the virus cannot replicate and cause infection in the person. However, until now, VLPs were not a viable solution, because the capsid protein was unstable in absence of the genetic material, and would lose its immunogenic properties at warmer temperatures. 

Adeyemi et al. selected thermally stable mutants of polio virus 1 (PV-1) by repeated thermal inactivation of the virus, then transferring surviving virus to a new culture and doing it again. This serial passage was repeated at increasing temperatures, until there were three pools of thermally selected viruses, VS51, VS53, and VS57, which were selections at 51, 53 and 57 degrees Celsius respectively. 

They conducted assays that showed that the thermally selected virus maintained infectivity at higher temperatures compared to the wild type. The thermally stable mutants had mutations in the hydrophobic pocket of capsid protein VP1, which is important for the uncoating step and is highly conserved in the three poliovirus serotypes. Other mutations included a mutated residue on the five-fold vertex, and mutations in surfaces between subunits of the capsid.

From a polio eradication perspective, having a VLP vaccine helps eliminate the issues involved in both the live attenuated polio vaccine and the inactivated polio vaccine. A VLP vaccine would eliminate the need to grow large quantities of live virus and attenuate it, which is the process for creating the live attenuated vaccine. In addition, the possibility of reversion to replication-competent form is eliminated, and we don't have to worry that vaccinated people may shed live virus and infect others. At the same time, it confers the same superior immunity as the live virus compared to the inactivated virus.

An interesting find for those studying virus structure: Some of the assays found that higher thermal stability of the virus may be correlated to how synchronous RNA release and the first protein melting event are. That is, the more thermally stable it is, the more likely these events are to happen in sync rather than at different times. This helps add to our understanding of the genetic basis for thermal stability of viral capsids.

Adeyemi OO., et al. "Increasing type-1 poliovirus capsid stability by thermal selection." Journal of Virology (2016): JVI-01586. 

Outbreak News Today

- Richa Wadekar

No comments: