Researchers at UC Davis have designed a new system which promises to make it safer to use viruses as vaccines. Viruses have great potential as vaccine vectors or in cancer therapy, given their ability to replicate within the body and an easily altered genome. One commonly used viral species, Vaccinia virus, is the focus of the UC Davis study, which attempts to address the threat of complications stemming from the viral infection itself. Generally, Vaccinia is not an overtly dangerous virus, but when introduced to immune-compromised individuals (which is common when it is used as a vaccine vector), it can lead to serious issues.
The study, published in the latest issue of the Proceedings of the National Academy of Sciences, looks to design a system where the viral infection has a sort of failsafe switch built in. The group inserted a gene for interferon-gamma into the virus’ genome, along with a regulatory gene that keeps the interferon from being produced except in the presence of tetracycline family antibiotics. What this means is that the researchers built in an inducible kill-switch for the viral infection, in case serious complications should arise from the viral infection itself. Simply treat the patient with any normal line of tetracycline family antibiotics and the virus will more or less bring about its own demise.
Interferon-gamma (or IFN-γ) is a compound which acts both as an antiviral in and of itself and as a stimulant for the immune system. In particular, it is known for triggering both non-specific macrophage action and the adaptive arm of the immune system, in the form of T and B cells. The study was carried out in severe combined immunodeficient mice, which have defects in the proteins necessary for DNA repair which make the adaptive immune process possible. This means that the effectiveness of their failsafe comes from its activation of a non-specific reaction in macrophages, ensuring that it is a viable treatment option in similarly compromised human immune systems.
The study demonstrated that those mice infected with the virus sporting antibiotic-triggered IFN-γ survived infection far better than those without the failsafe. This acts as a sort of proof-of-concept for viral vaccines that can be engineered for regulation through standard treatment processes. They labeled these new viral vaccines SMART VCVs (which stands for Safety Mechanism Assisted by the Repressor of Tetracycline Vaccinia virus), a fitting name for something so promising. This study promises the ability to use viral vaccines in a more aggressive fashion, while reducing the risk of serious complications arising from their use. Given how much damage these viruses can do in an immunocompromised individual (such as a cancer patient undergoing radiation), this could be a big step forward in a number of therapeutic fields.
Original article: http://www.pnas.org/content/110/38/15407.full