EFFECTS OF DNA-MLV PRIME BOOST IMMUNIZATION ON MODULATION OF PRRSV-SPECIFIC IMMUNE RESPONSES IN HP-PRRSV CHALLENGED PIGS

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) has been recognized as the important swine pathogen that threaten swine industry globally. The quasispesies character of PRRSV causes genetic variation, leading to the emergence of the new variant type 2 PRRSV, known as highly pathogenic PRRSV (HP-PRRSV). HP-PRRSV first emerged in China in 2006 and then spread to circulate in the Southeast Asia region. Currently, commercially available modified live PRRS vaccines (MLV) are not able to provide complete protection against the HP-PRRSV, and have been reported to induce negative immunomodulatory effects in vaccinated pigs. 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-g 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 complete 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.