Apa2H1, the first head domain of Apa2 trimeric autotransporter adhesin, activates mouse bone marrow-derived dendritic cells and immunization with Apa2H1 protects against Actinobacillus pleuropneumoniae infection

Mol Immunol. 2017 Jan:81:108-117. doi: 10.1016/j.molimm.2016.12.004. Epub 2016 Dec 7.

Abstract

Actinobacillus pleuropneumoniae is the causative pathogen of porcine pleuropneumonia, which results in large economic losses in the pig industry worldwide. There are, however, no effective subunit vaccines are available in the market owing to the various serotypes and the absence of cross-protection against this pathogen. Therefore, the selection of protective components is of great significance for vaccine development. We previously showed that trimeric autotransporter adhesins are important virulence factors of A. pleuropneumoniae. To determine the potential role in vaccine development of the functional head domain (Apa2H1) of Apa2, a trimeric autotransporter adhesin found in A. pleuropneumoniae, we obtained nature-like trimeric Apa2H1 using a prokaryotic expression system and co-culture of Apa2H1 with bone marrow derived dendritic cells (BMDCs) in vitro resulted in maturation of BMDCs, characterised by the up-regulation of CD83, MHC-II, CCR7, ICAM-I and the increased expression of factors related to B lymphoid cells stimulation, such as proliferation-inducing ligand (APRIL), B lymphocyte stimulator (BLyS) and B cell activating factor (BAFF). The in vivo results showed that vaccination with Apa2H1 resulted in the robust production of antigen-specific antibodies, modestly induced mixed Th1 and Th2 immunity, impaired bacterial colonization and dissemination, and improved mouse survival rates. This study is the first to show that Apa2H1 is antigenic and can be used as a component of a subunit vaccine against A. pleuropneumoniae infection, providing valuable reference material for the development of an effective vaccine against A. pleuropneumoniae.

Keywords: Actinobacillus pleuropneumoniae; Apa2H1; Protection; Trimeric autotransporter adhesion; Vaccination.

MeSH terms

  • Actinobacillus Infections / immunology*
  • Actinobacillus pleuropneumoniae / pathogenicity
  • Adhesins, Bacterial / immunology*
  • Animals
  • Bacterial Vaccines / immunology*
  • Blotting, Western
  • Bone Marrow Cells / immunology*
  • Dendritic Cells / immunology*
  • Disease Models, Animal
  • Female
  • Flow Cytometry
  • Mice
  • Mice, Inbred BALB C
  • Protein Domains
  • Real-Time Polymerase Chain Reaction
  • Vaccination
  • Vaccines, Subunit / immunology
  • Virulence Factors / immunology

Substances

  • Adhesins, Bacterial
  • Bacterial Vaccines
  • Vaccines, Subunit
  • Virulence Factors