Construction of a bivalent DNA vaccine co-expressing S genes of transmissible gastroenteritis virus and porcine epidemic diarrhea virus delivered by attenuated Salmonella typhimurium

Virus Genes. 2016 Jun;52(3):354-64. doi: 10.1007/s11262-016-1316-z. Epub 2016 Mar 15.

Abstract

Porcine transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV) can cause severe diarrhea in newborn piglets and led to significant economic losses. The S proteins are the main structural proteins of PEDV and TGEV capable of inducing neutralizing antibodies in vivo. In this study, a DNA vaccine SL7207 (pVAXD-PS1-TS) co-expressing S proteins of TGEV and PEDV delivered by attenuated Salmonella typhimurium was constructed and its immunogenicity in piglets was investigated. Twenty-day-old piglets were orally immunized with SL7207 (pVAXD-PS1-TS) at a dosage of 1.6 × 10(11) CFU per piglet and then booster immunized with 2.0 × 10(11) CFU after 2 weeks. Humoral immune responses, as reflected by virus neutralizing antibodies and specific IgG and sIgA, and cellular immune responses, as reflected by IFN-γ, IL-4, and lymphocyte proliferation, were evaluated. SL7207 (pVAXD-PS1-TS) simultaneously elicited immune responses against TGEV and PEDV after oral immunization. The immune levels started to increase at 2 weeks after immunization and increased to levels statistically significantly different than controls at 4 weeks post-immunization, peaking at 6 weeks and declined at 8 weeks. The humoral, mucosal, and cellular immune responses induced by SL7207 (pAXD-PS1-TS) were significantly higher than those of the PBS and SL7207 (pVAXD) (p < 0.01). In particular, the levels of IFN-γ and IL-4 were higher than those induced by the single-gene vaccine SL7207 (pVAXD-PS1) (p < 0.05). These results demonstrated that SL7207 (pVAXD-PS1-TS) possess the immunological functions of the two S proteins of TGEV and PEDV, indicating that SL7207 (pVAXD-PS1-TS) is a candidate oral vaccine for TGE and PED.

Keywords: Attenuated Salmonella typhimurium; Oral immunogenicity; Piglets; Porcine epidemic diarrhea; S protein; Transmissible gastroenteritis.

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • COS Cells
  • DNA, Recombinant / genetics
  • DNA, Recombinant / immunology
  • DNA, Viral / genetics
  • DNA, Viral / immunology
  • Gastroenteritis, Transmissible, of Swine / immunology
  • Gastroenteritis, Transmissible, of Swine / prevention & control
  • Genes, Viral
  • Immunoglobulin G / blood
  • Interferon-gamma / blood
  • Interleukin-4 / blood
  • Porcine epidemic diarrhea virus / genetics
  • Porcine epidemic diarrhea virus / immunology*
  • Salmonella typhimurium / genetics*
  • Salmonella typhimurium / immunology*
  • Swine
  • Transmissible gastroenteritis virus / genetics
  • Transmissible gastroenteritis virus / immunology*
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / genetics
  • Vaccines, Attenuated / immunology
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology*
  • Viral Proteins / genetics
  • Viral Proteins / immunology*
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • DNA, Recombinant
  • DNA, Viral
  • Immunoglobulin G
  • Vaccines, Attenuated
  • Vaccines, DNA
  • Viral Proteins
  • Viral Vaccines
  • spike protein S, Transmissible gastroenteritis virus
  • Interleukin-4
  • Interferon-gamma