African swine fever vaccine candidate ASFV-g-deltaI177l produced in the swine macrophage-derived cell line IPKM remains genetically stable and protective against homologous virulent challenge

Authors: Borca, Manuel; RAI, AYUSHI - Oak Ridge Institute For Science And Education (ORISE); Espinoza, Nallely; Ramirez-Medina, Elizabeth; Spinard Iii, Edward; Velazquez, Lauro; VALLADARES, ALYSSA - Oak Ridge Institute For Science And Education (ORISE); Silva, Ediane; Burton, Leeanna; MEYERS, AMANDA - Oak Ridge Institute For Science And Education (ORISE); Gay, Cyril; Gladue, Douglas

Submitted to: Viruses
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/1/2023
Publication Date: 10/8/2023
Citation: Borca, M.V., Rai, A., Espinoza, N.N., Ramirez Medina, E., Spinard III, E.J., Velazquez Salinas, L., Valladares, A., Silva, E.B., Burton, L.J., Meyers, A., Gay, C.G., Gladue, D.P. 2023. African swine fever vaccine candidate ASFV-g-deltaI177l produced in the swine macrophage-derived cell line IPKM remains genetically stable and protective against homologous virulent challenge. Viruses. 5(10). Article 2064. https://doi.org/10.3390/v15102064.
DOI: https://doi.org/10.3390/v15102064

Interpretive Summary: African swine fever, a devastating and deadly disease affecting domestic pigs, is widely spread in Eurasia producing significant economic problems in the pork industry. In this manuscript we discuss the evaluation of a new cell line that is derived from swine cells, that allows for growth of the African swine fever virus and live-attenuated vaccines without introducing undesirable genetic modifications.

Technical Abstract: ASFV vaccine candidate ASFV-G-I177L has been shown to be highly efficacious in inducing protection against challenge with the parental virus, the Georgia 2010 isolate, as well as against field strains isolated from Vietnam. ASFV-G-I177L has been shown to produce protection even when used at low doses (102 HAD50) and shows no residual virulence even when administered at high doses (106 HAD50) or evaluated for a relatively long period of time (6 months). ASFV-G-I177L stocks can only be massively produced in primary cell macrophages. Alternatively, its modified version (ASFV-G-I177L/LVR) grows in a swine derived cell line (PIPEC) acquiring significant genomic modifications. We present here the development of ASFV-G-I177L stocks in a swine macrophage cell line,IPKM, and its protective efficacy when evaluated in domestic pigs. Successive passing of ASFV-G-I177L in IPKM cells produce minimal genomic changes. Interestingly, a stock of ASFV-G-I177L obtained after 10 passages (ASFV-G-I177Lp10) in IPKM cells showed very small genomic changes when compared with the original virus stock. ASFV-G-I177Lp10 conserves similar grow kinetics in primary swine macrophages cultures than the original parental virus ASFV-G-I177L. Pigs infected with 103 HAD50 of ASFV-G-I177Lp10 developed a strong virus specific antibody response and were completely protected against the challenge with the parental virulent field isolate Georgia 2010. Therefore, IPKM cells could be an effective alternative for the production of ASFV vaccine stocks for those vaccine candidates exclusively growing in swine macrophages.