Induction of Robust Immune Responses in Swine by Using a Cocktail of Adenovirus-Vectored African Swine Fever Virus Antigens

Clin Vaccine Immunol. 2016 Nov 4;23(11):888-900. doi: 10.1128/CVI.00395-16. Print 2016 Nov.

Abstract

The African swine fever virus (ASFV) causes a fatal hemorrhagic disease in domestic swine, and at present no treatment or vaccine is available. Natural and gene-deleted, live attenuated strains protect against closely related virulent strains; however, they are yet to be deployed and evaluated in the field to rule out chronic persistence and a potential for reversion to virulence. Previous studies suggest that antibodies play a role in protection, but induction of cytotoxic T lymphocytes (CTLs) could be the key to complete protection. Hence, generation of an efficacious subunit vaccine depends on identification of CTL targets along with a suitable delivery method that will elicit effector CTLs capable of eliminating ASFV-infected host cells and confer long-term protection. To this end, we evaluated the safety and immunogenicity of an adenovirus-vectored ASFV (Ad-ASFV) multiantigen cocktail formulated in two different adjuvants and at two immunizing doses in swine. Immunization with the cocktail rapidly induced unprecedented ASFV antigen-specific antibody and cellular immune responses against all of the antigens. The robust antibody responses underwent rapid isotype switching within 1 week postpriming, steadily increased over a 2-month period, and underwent rapid recall upon boost. Importantly, the primed antibodies strongly recognized the parental ASFV (Georgia 2007/1) by indirect fluorescence antibody (IFA) assay and Western blotting. Significant antigen-specific gamma interferon-positive (IFN-γ+) responses were detected postpriming and postboosting. Furthermore, this study is the first to demonstrate induction of ASFV antigen-specific CTL responses in commercial swine using Ad-ASFV multiantigens. The relevance of the induced immune responses in regard to protection needs to be evaluated in a challenge study.

MeSH terms

  • Adenoviridae / genetics
  • African Swine Fever Virus / immunology*
  • Animals
  • Antigens, Viral / chemistry
  • Antigens, Viral / immunology*
  • Genetic Vectors
  • Immunity, Cellular*
  • Immunogenicity, Vaccine*
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Swine
  • T-Lymphocytes, Cytotoxic / immunology
  • Vaccines, Subunit / adverse effects
  • Vaccines, Subunit / immunology
  • Viral Vaccines / adverse effects
  • Viral Vaccines / immunology*
  • Virulence

Substances

  • Antigens, Viral
  • Vaccines, Subunit
  • Viral Vaccines
  • Interferon-gamma