title: A novel DNA vaccine for reduction of PRRSV-induced negative immunomodulatory effects: A proof of concept.
abstract: BACKGROUND
  Viral-induced interleukin (IL)-10 and regulatory T lymphocytes (Tregs) are believed to play a major role in shaping the immunological and clinical outcomes following Porcine Reproductive and Respiratory Syndrome virus (PRRSV) infection. Recently, it has been shown that PRRSV nucleocapsid (N) protein can induce IL-10 production which is essential for induction of PRRSV-specific Tregs. We hypothesized that immunity to N protein should reduce PRRSV-induced negative immunomodulatory effects which will be essential for establishing proper anti-PRRSV immunity in infected pigs.
  
  
  OBJECTIVE
  To investigate the immunomodulatory effects of DNA vaccine encoding a linearized, truncated form of PRRSV-N protein (pORF7t) which was designed to preferentially induce cell-mediated immunity against PRRSV N protein.
  
  
  METHODS
  Immunomodulatory effects of the novel DNA vaccine were investigated in an experimental vaccinated-challenged model. In addition, long-term immunomodulatory effects of the DNA vaccine were investigated in vaccinated pigs kept at the PRRSV-positive environment until the end of the fattening period. Pigs were vaccinated either prior to or following natural PRRSV infection.
  
  
  RESULTS
  The results indicated that pORF7t could modulate the anti-PRRSV immune responses and promote the control of viral replication in the vaccinated-challenged pigs. Immunized pigs exhibited increased numbers of PRRSV-specific activated CD4(+)CD25(+) lymphocytes, reduced numbers of PRRSV-specific Tregs, and rapid viral clearance following infection. In a long-term study, regardless of the time of vaccination, DNA vaccine could modulate the host immune responses, resulted in enhanced PRRSV-specific IFN-γ producing cells, and reduced numbers of PRRSV-specific Tregs, without evidence of enhanced antibody responses. No vaccine adverse reaction was observed throughout the study.
  
  
  CONCLUSIONS
  This study revealed the novel concept that PRRSV-specific immunity can be modulated by induction of cell-mediated immunity against the nucleocapsid protein. This concept could potentially benefit the development of PRRSV management and control strategies.
authors.affiliation: Faculty of Veterinary Science, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand; Center of Excellence in Emerging Infectious Diseases in Animals, Chulalongkorn University (CU-EIDAs), Pathumwan, Bangkok 10330, Thailand. Electronic address: Sanipa.S@chula.ac.th.
authors.forename: Sanipa
authors.initials: S
authors.lastname: Suradhat
authors.affiliation: Inter-department of Medical Microbiology, Graduate School, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand.
authors.forename: Piya
authors.initials: P
authors.lastname: Wongyanin
authors.affiliation: Faculty of Veterinary Science, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand.
authors.forename: Sawang
authors.initials: S
authors.lastname: Kesdangsakonwut
authors.affiliation: Faculty of Veterinary Science, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand.
authors.forename: Komkrich
authors.initials: K
authors.lastname: Teankum
authors.affiliation: Thai-Denmark Swine Breeder Public Company Limited, Bang-na, Bangkok 10260, Thailand.
authors.forename: Mongkol
authors.initials: M
authors.lastname: Lumyai
authors.affiliation: Thai-Denmark Swine Breeder Public Company Limited, Bang-na, Bangkok 10260, Thailand.
authors.forename: Sittikorn
authors.initials: S
authors.lastname: Triyarach
authors.affiliation: Faculty of Veterinary Science, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand; Center of Excellence in Emerging Infectious Diseases in Animals, Chulalongkorn University (CU-EIDAs), Pathumwan, Bangkok 10330, Thailand.
authors.forename: Roongroje
authors.initials: R
authors.lastname: Thanawongnuwech
mesh_terms: D000818:Animals; D007108:Immune Tolerance; D008297:Male; D019590:Nucleocapsid Proteins / Q000235:genetics / Q000276:immunology*; D019318:Porcine Reproductive and Respiratory Syndrome / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D019316:Porcine respiratory and reproductive syndrome virus / Q000276:immunology*; D013552:Swine; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D019590:Nucleocapsid Proteins; D019444:Vaccines, DNA
keywords: DNA vaccine; Nucleocapsid protein; PRRSV; Tregs