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

PLoS Pathog. 2022 Nov 9;18(11):e1010931. doi: 10.1371/journal.ppat.1010931. eCollection 2022 Nov.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • African Swine Fever Virus*
  • African Swine Fever*
  • Animals
  • Immunity, Innate
  • Sus scrofa
  • Swine
  • Vaccination
  • Viral Proteins
  • Viral Vaccines*

Substances

  • Viral Proteins
  • Viral Vaccines

Grants and funding

This work has been funded by the Spanish Ministry of Science and Innovation [grant PID2019-107616RB-I00 (FR)], ISCIII/MINECO [grant PT17/0009/0019, cofunded by FEDER (AEC)], Huvepharma (FR, BG), and the Swedish Research Council for Environment [Agricultural Sciences and Spatial Planning (FORMAS), grant 2017-00486 (LL)]. Huvepharma participated in the study design of the first animal experiment.