Horsepox Virus: An Example of Synthetic Virology

Smallpox virions. Photo by Dr. Fred Murphy via Wikimedia Commons. 

Smallpox first emerged in North-east Africa more than 12,000 years ago. Outbreaks in the fifth and seventh centuries caused mass devastation, but there was one significant favourable outcome for survivors: immunity from re-infection. Edward Jenner (1749-1823) is often credited for the creation of the smallpox vaccine, although the practice of inoculation began long before the 18th century. Jenner observed that dairy maids infected with a mild skin disease called “cowpox” were immune to smallpox. Jenner collected material from a dairy maid’s lesions and injected it into a young boy (obviously, there was no informed consent in those days!). The boy developed a slight fever, but he quickly recovered. Several weeks later, Jenner directly inoculated the boy with material from a human smallpox lesion! The boy was immune, and no disease developed. Jenner didn’t understand viruses at all, and it would be 100 more years before Dutch microbiologist Martinus Beijerinck would coin the term ‘virus’ to describe an infectious agent small enough to pass through a filter. Nevertheless, using his powers of observation, Jenner was able to create a very successful vaccine.

Synthetic virology is a new area of research that employs advanced genetic techniques to make precisely-engineered viruses. The recent emergence of this field is due to a revolution in our ability to design, synthesize, and manipulate large chunks of DNA. Thus, we can build whole virus genomes and easily re-code portions of the genome to test the properties of viral genes. This approach has big implications for vaccines; with synthetic virology we can rapidly build and test new vaccine strains with targeted mutations that increase efficacy, safety, shelf-life, and heat-tolerance.

Despite the eradication of smallpox worldwide in 1977, we still need smallpox vaccines to guard against potential outbreaks. The vaccinia virus used to eradicate smallpox was long thought to be derived from a natural cowpox virus, but recent genetic studies revealed that it more closely resembles a horsepox virus that no longer circulates in the wild. For this reason, Noyce R. et. al.  used synthetic virology to create a horsepox virus that could be used as a superior and safer smallpox vaccine alternative to vaccinia virus. This work builds on previous efforts to make synthetic poliovirus, herpes simplex virus, and cytomegalovirus genomes, all of which were used to study the properties of viral genes and figure out ways to make better vaccines. In this study, the researchers used a mouse model to test the effectiveness and safety of their horsepox-derived vaccine. The vaccine appeared safe, as it did not cause illness in the mice. In addition, the vaccine offered protection after exposure to a normally lethal dose of smallpox. The research described in this article provides rationale for the continued exploration of a horsepox-based vaccine to replace the current smallpox vaccine.

We would love to you know thoughts. This blog post briefly touches on the ethical implications of their work, what do you think needs to be considered before a researcher is allowed to synthesize a virus? What safe-guards should be in place? Comment below!

Summary written by: Serena Drouillard & Emma Finlayson-Trick

To read the full article, please click the following link:

Construction of an infectious horsepox virus vaccine from chemically synthesized DNA fragments

Ryan S. Noyce, Seth Lederman, David H. Evans

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