Cellular and Humoral Immune Responses after Immunisation with Low Virulent African Swine Fever Virus in the Large White Inbred Babraham Line and Outbred Domestic Pigs

Abstract

African swine fever virus is currently present in all of the world’s continents apart from Antarctica, and efforts to control the disease are hampered by the lack of a commercially available vaccine. The Babraham large white pig is a highly inbred line that could represent a powerful tool to improve our understanding of the protective immune responses to this complex pathogen; however, previous studies indicated differential vaccine responses after the African swine fever virus challenge of inbred minipigs with different swine leukocyte antigen haplotypes. Lymphocyte numbers and African swine fever virus-specific antibody and T-cell responses were measured in inbred and outbred animals after inoculation with a low virulent African swine fever virus isolate and subsequent challenge with a related virulent virus. Surprisingly, diminished immune responses were observed in the Babraham pigs when compared to the outbred animals, and the inbred pigs were not protected after challenge. Recovery of Babraham pigs after challenge weakly correlated with antibody responses, whereas protective responses in outbred animals more closely correlated with the T-cell response. The Babraham pig may, therefore, represent a useful model for studying the role of antibodies in protection against the African swine fever virus.

African Swine Fever Virus Infection and Cytokine Response In Vivo: An Update

“…Nevertheless, in some studies, high numbers of IFN-γ-producing cells did not always correlate to animal survival after challenge, indicating that induction of IFN-γ-specific T cells is not a sufficient indicator of protection either when virulent challenges were carried out shortly after immunizations [ 80 , 81 , 82 ] or when they were performed long after immunizations [ 59 ], which suggests the existence of other mechanisms, although without excluding this one, that would be involved in the protection afforded by different ASFV attenuated isolates [ 20 , 21 , 22 , 83 ]. Adenovirus, alphavirus and vaccinia virus vectors have all been shown to induce effective ASFV antigen-specific responses.…”

“…So far, few pioneering studies have been carried out. Phenotyping of ASFV-specific IFN-γ-producing cells in pigs after immunization with BeninΔMGF and OURT88/3 have been fully characterized [ 59 , 82 ]. In both studies, the authors observed that the source of IFN-γ in both immunized groups originated from different subsets of CD8 + T cells, mainly cytotoxic (CD8 high ) T cells, particularly double-positive memory (CD4 + CD8 + ) T cells, suggesting a possible role of these cells in protection.…”

“…In both studies, the authors observed that the source of IFN-γ in both immunized groups originated from different subsets of CD8 + T cells, mainly cytotoxic (CD8 high ) T cells, particularly double-positive memory (CD4 + CD8 + ) T cells, suggesting a possible role of these cells in protection. Moreover, they highlighted the importance of other IFN-γ-secreting cells in these mechanisms, such as γδ-T cells or NK cells [ 59 , 82 ]. Goatley et al [ 82 ] observed how increased numbers of specific IFN-γ + cells evaluated after the inoculation with the attenuated isolate OURT88/3 in both inbred and outbred pigs did not serve as a protection indicator against challenge with the virulent isolate OURT88/1, and suggested a possible role of antibodies in protection against homologous virulent isolates.…”

“…Moreover, they highlighted the importance of other IFN-γ-secreting cells in these mechanisms, such as γδ-T cells or NK cells [ 59 , 82 ]. Goatley et al [ 82 ] observed how increased numbers of specific IFN-γ + cells evaluated after the inoculation with the attenuated isolate OURT88/3 in both inbred and outbred pigs did not serve as a protection indicator against challenge with the virulent isolate OURT88/1, and suggested a possible role of antibodies in protection against homologous virulent isolates. However, differences in the cellular responses (mainly of CD8 + T cells) in outbred pigs that survived a second challenge with the genotype II virulent isolate Georgia 2007/1 were observed [ 82 ].…”

“…Goatley et al [ 82 ] observed how increased numbers of specific IFN-γ + cells evaluated after the inoculation with the attenuated isolate OURT88/3 in both inbred and outbred pigs did not serve as a protection indicator against challenge with the virulent isolate OURT88/1, and suggested a possible role of antibodies in protection against homologous virulent isolates. However, differences in the cellular responses (mainly of CD8 + T cells) in outbred pigs that survived a second challenge with the genotype II virulent isolate Georgia 2007/1 were observed [ 82 ]. In a recent work, both flow cytometry and gene expression analysis were employed to characterize ASFV-specific cytokine-producing cells in domestic pigs immunized with BA71ΔCD2, a candidate vaccine that conferred dose-dependent cross-protection against direct-contact challenge with pigs infected with the genotype II virulent isolate Georgia2007/1.…”