Cross-protection against African swine fever virus upon intranasal vaccination is associated with an adaptive-innate immune crosstalk

Abstract

African swine fever virus (ASFV) is causing a worldwide pandemic affecting the porcine industry and leading to important global economic consequences. The virus causes a highly lethal hemorrhagic disease in wild boars and domestic pigs. Lack of effective vaccines hampers the control of virus spread, thus increasing the pressure on the scientific community for urgent solutions. However, knowledge on the immune components associated with protection is very limited. Here we characterized the in vitro recall response induced by immune cells from pigs intranasally vaccinated with the BA71ΔCD2 deletion mutant virus. Vaccination conferred dose-dependent cross-protection associated with both ASFV-specific antibodies and IFNγ-secreting cells. Importantly, bulk and single-cell transcriptomics of blood and lymph node cells from vaccinated pigs revealed a positive feedback from adaptive to innate immunity. Indeed, activation of Th1 and cytotoxic T cells was concomitant with a rapid IFNγ-dependent triggering of an inflammatory response characterized by TNF-producing macrophages, as well as CXCL10-expressing lymphocytes and cross-presenting dendritic cells. Altogether, this study provides a detailed phenotypic characterization of the immune cell subsets involved in cross-protection against ASFV, and highlights key functional immune mechanisms to be considered for the development of an effective ASF vaccine.

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

“…Some correlation between virus-specific IFN-γ-producing cells induced after immunization with BeninΔDP148R and protection against the virulent parental Benin97/1 was also observed [ 54 ]. In addition, correlation between protection and ASFV-specific IFN-γ-producing cells was recently reported [ 79 ]. In detail, the immunization of pigs with the BA71ΔCD2 deletion mutant (developed from the virulent genotype I Badajoz-71) conferred dose-dependent cross-protection against direct-contact challenge with pigs infected with the genotype II virulent isolate Georgia2007/1.…”

“…In detail, the immunization of pigs with the BA71ΔCD2 deletion mutant (developed from the virulent genotype I Badajoz-71) conferred dose-dependent cross-protection against direct-contact challenge with pigs infected with the genotype II virulent isolate Georgia2007/1. Protection was associated with IFNγ-secreting cells, evaluated by ELIspot in PBMC (re-stimulated ex vivo with either BA71ΔCD2 or Georgia2007/1) [ 79 ].…”

“…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. Researchers reported that intracellular cytokine staining of PBMC from BA71ΔCD2-immunized pigs, stimulated ex vivo with BA71ΔCD2, showed elevated percentages of ASFV-specific IFNγ- and TNF-producing CD4 + CD8 + T cells, a phenotype characteristic of polyfunctional memory T cells [ 79 ]. In the same work, researchers employed bulk and single-cell transcriptomics to characterize immune responses against the deleted mutant BA71ΔCD2.…”

“…In the same work, researchers employed bulk and single-cell transcriptomics to characterize immune responses against the deleted mutant BA71ΔCD2. Transcriptomics carried out on PBMC showed that BA71ΔCD2 triggered ASFV-specific activation of Th1 and cytotoxic T cells, concomitant with a rapid IFNγ-dependent triggering of an inflammatory response characterized by TNF-producing macrophages [ 79 ].…”

“…Several cell populations were significantly overrepresented in lymph node cells from the vaccinated pig Interestingly, the proinflammatory CXCL10 chemokine was strongly upregulated in plasmablasts, in the undefined CD4 + T cell subset and in cross-presenting DCs, thus further validating the induction of a Th1-biased recall response. In the sample from the vaccinated pig, cytotoxic T lymphocytes showed downregulation of CCR7 and CXCR4, a hallmark of differentiation to effector CD8 T cells [ 79 ].…”