The virus reconstruction project – detailed in a study in the journal Science – was prompted in part by an interest in horsepox’s role in the history of vaccine development according to lead researcher David Evans.
“It has been suggested that vaccinia virus (the virus used to vaccinate against smallpox) might have been isolated from cows infected with horsepox virus,” he told Biopharma-Reporter.
“This is supported by old experiments from the early 19th century and by modern genome sequencing. We are interested in studying this historical connection between vaccinia and horsepox viruses.”
The researchers used a combination of DNA cloning and a publicly available horsepox genome sequence to reconstruct the virus.
“These were linearized, the appropriate ends added to each of the telomeric fragments, and transfected into cells previously infected with a helper virus.”
“The helper virus catalyses DNA replication and recombination reactions that leads to the assembly of small numbers of infectious particles derived from the transfected DNAs. These ‘reactivated’ viruses are then recovered by plaque purification,” he said.
The reconstructed horsepox virus has potential application in the production of vaccines and in biomanufacturing according to Evans.
“We also think that the horsepox virus might be a safer virus vaccine and provide a new platform for the expression of recombinant proteins,” he said.
Evans said this could not only enable the development of vaccines against other diseases, but potentially aid the development of viruses that can kill tumours.
Despite the eradication of the smallpox virus in 1980, recently interest in the virus shows maintained market demand for vaccines against the smallpox.
Earlier this year, Canadian firm Tonix developed a live-virus vaccine for smallpox, developed in pre-clinical stages by Evans and Ryan Noyce at the University of Alberta.
As recently as yesterday, Emergent BioSolutions announced it will purchase Sanofi’s smallpox vaccine ACAM2000, which was approved by the US Food and Drug Administration in 2007.
A viral threat?
Evans told us that although animals may still be vulnerable to the horsepox virus, the team is confident that it poses no risk to humans.
“Horsepox virus has not been studied much, but our evidence suggests it behaves like a highly attenuated vaccinia virus. Therefore we treat it as a level 2 agent from a human health perspective.”
“We presume it could still be a hazard to animals, although horsepox as a disease attracted so little notice that it may have gone extinct without anyone really noticing,” he said.
However, while the horsepox virus itself may not be a threat, Evans told us the approach used to resurrect it could be applied to any orthopoxcirus virus, including smallpox.
“This would be a hazard to human health unless stringent controls are kept in place to restrict the synthesis of variola virus DNA,” he said.