Association of the host immune response with protection using a live attenuated African swine fever virus model

Authors: CARLSON, JOLENE - Kansas State University; O'DONNELL, VIVIAN - University Of Connecticut; ALFANO, MARIALEXIA - Oak Ridge Institute For Science And Education (ORISE); VELAZQUEZ-SALINAS, LAURO - Oak Ridge Institute For Science And Education (ORISE); Holinka-Patterson, Lauren; Krug, Peter; Gladue, Douglas; HIGGS, STEPHEN - Kansas State University; Borca, Manuel

Submitted to: Viruses
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/16/2016
Publication Date: 10/22/2016
Citation: Carlson, J., O'Donnell, V.K., Alfano, M., Velazquez-Salinas, L., Holinka-Patterson, L.G., Krug, P.W., Gladue, D.P., Higgs, S., Borca, M.V. 2016. Association of the host immune response with protection using a live attenuated African swine fever virus model . Viruses. 8(10):E291. https://doi.org/10.3390/v8100291.
DOI: https://doi.org/10.3390/v8100291

Interpretive Summary: African swine fever virus (ASFV) causes a lethal disease of swine. Infection with attenuated strains protect against challenge but there is limited knowledge of the immune mechanisms generating that protection. The manuscript reports our efforts in identifying host immune mechanism mediating protection in ASFV. We present here a model based in animals immunized with an attenuated virus strain called ASFV Pret4 delta 9GL, which were further challenged at different times post immunization. We tried to correlate presence of different host immune mechanism, such as the presence of virus-specific antibodies or interferon response, with protection against challenge. Our results, based in data obtained from over 60 animals, suggest that while antibodies may facilitate protection at late times post vaccination, the mechanism mediating early protection after vaccination remain elusive. These results underscore the complexity of ASFV and suggests that protection involves the concurrence of different host immune mechanisms.

Technical Abstract: African swine fever virus (ASFV) causes a lethal disease of swine. Infection with attenuated strains protect against challenge but there is limited knowledge of the immune mechanisms generating that protection. ASFV Pret4 produces a fatal disease, while its derivative, lacking virulence-associated gene 9GL (ASFV Pret4 delta 9GL) is attenuated. Swine infected with ASFV Pret4 delta 9GL and challenged with ASFV Pret4 at 7,10, 14, 21, and 28 dpi showed a progressive acquisition of protection. This animal model was used to associate the presence of host immune response (ASFV-specific antibody and IFN-gamma responses, or specific cytokine profiles) and protection against challenge. With the exception of ASFV-specific antibodies in survivors challenged at 21 and 28 dpi, no association between the parameters assessed and protection could be established. These results, encompassing data from 65 immunized swine, underscore the complexity of the system under study suggesting that protection relies on the concurrence of different host immune mechanisms.