Identification of genetic deletions in ASFV that could be potentially used as targets for the development of DIVA vaccines

Authors: VUONO, ELIZABETH - Mississippi State University; Ramirez-Medina, Elizabeth; Silva, Ediane; RAI, AYUSHI - Oak Ridge Institute For Science And Education (ORISE); Pruitt, Sarah; Espinoza, Nallely; Velazquez, Lauro; Borca, Manuel; Gladue, Douglas

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 10/4/2021
Publication Date: 1/12/2022
Citation: Vuono, E., Ramirez Medina, E., Silva, E.B., Rai, A., Pruitt, S.E., Espinoza, N.N., Velazquez Salinas, L., Borca, M.V., Gladue, D.P. 2022. Identification of genetic deletions in ASFV that could be potentially used as targets for the development of DIVA vaccines. Meeting Abstract. https://doi.org/10.1128/JVI.01419-21.
DOI: https://doi.org/10.1128/JVI.01419-21

Interpretive Summary:

Technical Abstract: African swine fever virus (ASFV) is responsible for an on-going pandemic. We assessed the role of two different genetic DIVA candidate genes E184L the MGF110-5L-6L and their addition to different vaccine candidates. 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. All animals surviving ASFV-G-'E184L infection developed a strong virus specific 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 strongly recognized them. These results demonstrates that E184L 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 differentiate infected from vaccinated animals (DIVA). A recombinant virus with a deletion of MGF110-5L-6L (ASFV-G-'MGF110-5L-6L) was developed using the highly virulent ASFV Georgia (ASFV-G) isolate as a template. ASFV-G-'MGF110-5L-6L replicates in swine macrophage cultures as efficiently as the parental virus ASFV-G, indicating the MGF110-5L-6L gene is non-essential for virus replication. Similarly, domestic pigs inoculated with ASFV-G-'MGF110 5.6 presented with a clinical disease undistinguishable from that caused by the parental ASFV-G, confirming the MGF110-5L-6L gene is not involved in producing disease in swine. Sera from animals inoculated with an efficacious vaccine candidate, ASFV-G-'MGF, strongly recognized the protein encoded by the MGF110-5L-6L gene indicating that it could be a potential target for the development of an antigenic marker DIVA vaccine. To test both this hypothesis, the MGF110-5L-6L gene was deleted from the highly efficacious ASFV vaccine candidate ASFV-G-'I177L, and the efficacy and DIVA capability of the resulting virus, ASFV-G-'I177L/'MGF110-5L-6L were assessed in domestic pigs.