Experimental vaccine for African swine fever virus shows promise
Researchers have discovered a previously uncharacterized virus gene, which when deleted completely attenuates the Georgia isolate (ASFV-G) of African swine fever virus. Animals infected with this genetically modified virus were protected from developing ASF after challenge with the virulent parental virus. The findings are reported in the Journal of Virology.
In the study, both low and high doses of the vaccine were 100% effective against the virus when the pigs were challenged 28 days post-inoculation.
The research was motivated by the 2007 outbreak of African swine fever in the Republic of Georgia, said principal investigator Douglas P. Gladue, Senior Scientist, Plum Island Animal Disease Center, Agricultural Research Service, US Department of Agriculture. “This was the first outbreak in recent history outside of Africa and Sardinia — where swine fever is endemic — and this particular strain has been highly lethal and highly contagious, spreading quickly to neighbouring countries.”
The 2007 outbreak was also the genesis of the African swine fever that has been spreading through Eastern Europe and east Asia, said Manuel V. Borca, also a Senior Scientist at the Plum Island Animal Disease Center.
There is limited cross-protection between strains of African swine fever virus, likely because the antigens and degree of virulence differ among them, and none of the historical experimental vaccines have been shown to be effective against ASFV-G, said Dr. Gladue.
The investigators at Plum Island Animal Disease Center set out to develop a vaccine. Part of the process of developing whole virus vaccines involves deleting virulence genes from the virus. But when the researchers deleted genes similar to those that had been deleted in older ASFV strains to attenuate them, “it became clear that ASFV-G was much more virulent” than the other, historical isolates, because it retained a higher level of virulence, said Dr. Gladue. The investigators realized they needed a different genetic target in order to attenuate ASFV-G.
They used a predictive methodology — a computational pipeline — to predict the roles of proteins on the virus. The computational pipeline predicted that a protein called I177L could interfere with the immune system of the pig. When they deleted this gene, ASFV-G was completely attenuated.
More work needs to be done to meet regulatory requirements for commercialization, said Dr. Gladue. But “This new experimental ASFV vaccine shows promise, and offers complete protection against the current strain currently producing outbreaks throughout Eastern Europe and Asia.”
Article: Borca, M.V., Ramirez-Medina, E., Silva, E., Vuono, E., Rai, A., Pruitt, S., Holinka, L.G., Velazquez-Salinas, L., Zhu, J., Gladue, D.P. (2020). Development of a highly effective African swine fever virus vaccine by deletion of the I177L gene results in sterile immunity against the current epidemic Eurasia strain. Journal of Virology, doi: 10.1128/JVI.02017-19 [Epub ahead of print]
[SOURCE: American Society for Microbiology]