title: Positive immunomodulatory effects of heterologous DNA vaccine- modified live vaccine, prime-boost immunization, against the highly-pathogenic PRRSV infection.
abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) infection is one of the most important swine pathogens, and causes a major economic impact worldwide. Recently, a new variant type 2 PRRSV, highly pathogenic PRRSV (HP-PRRSV) has emerged and continued to circulate in Southeast Asia region. Currently, commercially available PRRSV vaccines, modified live PRRS vaccines (MLV) are not able to provide complete protection against HP-PRRSV and been reported to induce negative immunomodulatory effects. Interestingly, a novel DNA vaccine was developed and successfully used to improve PRRSV-specific immune responses following MLV vaccination. To investigate the efficacy of a heterologous DNA-MLV prime-boost immunization against the HP-PRRSV infection, an experimental vaccinated-challenged study was conducted. Two-week-old, PRRSV-seronegative, crossbred pigs (5-8 pigs/group) were allocated into 5 groups. At day -14 (D-14), the treatment group (DNA-MLV) was immunized with a DNA vaccine encoding PRRSV-truncated nucleocapsid protein (pORF7t), followed by a commercial modified live type 2 PRRS vaccine (MLV) at D0. The other groups included the group that received PBS at D-14 followed by MLV at D0 (MLV), pORF7t at D-14 (DNA), PBS at D0 (PBS) and the negative control group. At D42, all groups, except the negative control group, were challenged with HP-PRRSV (strain 10PL1). The results demonstrated that pigs that received MLV, regardless of the DNA priming, exhibited less clinical signs and faster viral clearance. Following HP-PRRSV challenge, the DNA-MLV group exhibited improved PRRSV-specific immunity, as observed by increased neutralizing antibody titers and PRRSV-specific IFN-γ production, and reduced IL-10 and PRRSV-specific Treg productions. However, neither the prime-boost immunization nor the MLV was able to induce complete clinical protection against HP-PRRSV infection. In conclusion, improved immunological responses, but not clinical protection, were achieved by DNA-MLV prime-boost immunization. This study highlights the potential use of heterologous prime-boost vaccination regimen, where DNA can be incorporated with other vaccine candidates, for improving anti-PRRSV immunity that may eventually lead induction of complete PRRSV protection.
authors.affiliation: Graduate Program in Veterinary Pathobiology, Faculty of Veterinary Science, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand.
authors.forename: Chaitawat
authors.initials: C
authors.lastname: Sirisereewan
authors.affiliation: Interdisciplinary Program in Medical Microbiology, Graduate School, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand.
authors.forename: Teerawut
authors.initials: T
authors.lastname: Nedumpun
authors.affiliation: Faculty of Veterinary Science, Chulalongkorn University, Pathumwan Bangkok 10330, Thailand.
authors.forename: Sawang
authors.initials: S
authors.lastname: Kesdangsakonwut
authors.affiliation: Graduate Program in Veterinary Pathobiology, Faculty of Veterinary Science, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand.
authors.forename: Yonlayong
authors.initials: Y
authors.lastname: Woonwong
authors.affiliation: Graduate Program in Veterinary Pathobiology, Faculty of Veterinary Science, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand.
authors.forename: Roongtham
authors.initials: R
authors.lastname: Kedkovid
authors.affiliation: Graduate Program in Veterinary Pathobiology, Faculty of Veterinary Science, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand.
authors.forename: Jirapat
authors.initials: J
authors.lastname: Arunorat
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
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
mesh_terms: D000818:Animals; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007117:Immunization, Secondary / Q000662:veterinary; D000071497:Immunogenicity, Vaccine; D019318:Porcine Reproductive and Respiratory Syndrome / Q000473:pathology / Q000517:prevention & control*; D019316:Porcine respiratory and reproductive syndrome virus / Q000276:immunology; D013552:Swine; D014613:Vaccines, Attenuated / Q000008:administration & dosage; D019444:Vaccines, DNA / Q000008:administration & dosage*
chemical_list: D014613:Vaccines, Attenuated; D019444:Vaccines, DNA
keywords: DNA vaccine; HP-PRRSV; Modified live PRRS vaccine; Prime-boost immunization