Deletion of E184L, a Putative DIVA Target from the Pandemic Strain of African Swine Fever Virus, Produces a Reduction in Virulence and Protection against Virulent Challenge

Authors: Ramirez-Medina, Elizabeth; VUONO, ELIZABETH - University Of Mississippi; RAI, AYUSHI - Oak Ridge Institute For Science And Education (ORISE); Pruitt, Sarah; Espinoza, Nallely; Velazquez, Lauro; PINA-PEDRERO, SONIA - Animal Health Centre; Zhu, James; RODRIGUEZ, FERNANDO - Oak Ridge Institute For Science And Education (ORISE); Borca, Manuel; Gladue, Douglas

Submitted to: Viruses
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/4/2021
Publication Date: 10/8/2021
Citation: Ramirez Medina, E., Vuono, E., Rai, A., Pruitt, S.E., Espinoza, N.N., Velazquez Salinas, L., Pina-Pedrero, S., Zhu, J.J., Rodriguez, F., Borca, M.V., Gladue, D.P. 2021. Deletion of E184L, a putative DIVA target from the pandemic strain of African Swine Fever Virus, produces a reduction in virulence and protection against virulent challenge. Viruses. https://doi.org/10.1128/JVI.01419-21.
DOI: https://doi.org/10.1128/JVI.01419-21

Interpretive Summary: African swine fever virus (ASFV) causes a devastating disease in swine, called African swine fever (ASF), that is currently spreading across Europe and Asia. here we test the ability of a recombinant virus with the gene E184L deleted, which has a reduction in virus virulence. We also add this deletion to our current ASFV vaccine candidate, however addition of this additional deletion decreases the vaccines level of protection against virulent challenge.

Technical Abstract: African swine fever (ASF) is currently causing a major pandemic affecting the swine industry and protein availability from Central Europe to East and South Asia. No commercial vaccines are available, making disease control dependent on the elimination of affected animals. Here, we show that the deletion of the African swine fever virus (ASFV) E184L gene from the highly virulent ASFV Georgia 2010 (ASFV-G) isolate produces a reduction in virus virulence during the infection in swine. Of domestic pigs intramuscularly inoculated with a recombinant virus lacking the E184L gene (ASFV-G-'E184L), 40% experienced a significantly (5 days) delayed presentation of clinical disease and, overall, had a 60% rate of survival compared to animals inoculated with the virulent parental ASFV-G. Importantly, all animals surviving ASFV-G-'E184L infection developed a strong antibody response and were protected when challenged with ASFV-G. As expected, a pool of sera from ASFV-G-'E184L-inoculated animals lacked any detectable antibody response to peptides partially representing the E184L protein, while sera from animals inoculated with an efficacious vaccine candidate, ASFV-G-'MGF, strongly recognize the same set of peptides. These results support the potential use of the E184L deletion for the development of vaccines able to differentiate infected from vaccinated animals (DIVA). Therefore, it is shown here that the E184L gene is a novel ASFV determinant of virulence that can potentially be used to increase safety in preexisting vaccine candidates, as well as to provide them with DIVA capabilities. To our knowledge, E184L is the first ASFV gene product experimentally shown to be a functional DIVA antigenic marker.