Positive Inductive Effect of Swine Interleukin-4 on Immune Responses Elicited by Modified Live Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Vaccine

Abstract

Porcine reproductive and respiratory syndrome (PRRS) has become one of the most economically important diseases to the global pork industry. Currently, the efficacies of available commercial vaccines remain questionable: the modified live-PRRSV vaccines (MLVs) were generally effective but variable in sufficient protection, and the outcomes of inactivated-PRRSV vaccines (IVs) in the field were not very promising. In the present study, we investigated the effect of swine interleukin 4 (IL-4) on the development of virus-specific immune responses elicited by an MLV. The antibody titer against PRRSV membrane proteins in pigs elicited by MLV plus recombinant plasmid encoding IL-4 (group 3) was significantly higher than those elicited by MLV alone (group 1) and MLV plus empty plasmid (group 2) from 35 days post-inoculation (dpi). Similarly, the neutralizing efficacy of sera from group 3 was markedly enhanced compared with group 1 and group 2. In cellular immunity, the ratio of CD3⁺CD4⁺/CD3⁺CD8⁺ T lymphocyte subpopulations from group 3 monitored by flow cytometry (FCM) was significantly higher than those from group 1 and group 2 from 42 dpi to 21 days post-challenge (dpc). After viral challenge, pigs in group 3 showed significantly lower virus loads in peripheral blood measured by a real-time quantitative PCR (RT-qPCR), as compared with those in group 1 and group 2. Pigs in group 1 and group 2 had a low fever and displayed mild inappetence, lethargy, rough hair coats, and no lung lesions, while those in group 3 showed almost no clinical signs, no lung lesions. The scores of clinical signs of pigs in group 3 were significantly lower than those in both group 1 and group 2. Interestingly, the scores of lung lesions showed no significant differences among the three groups. Our results indicate that swine IL-4 markedly enhanced the protective immune response of pigs and improved the efficacy of the MLV in preventing PRRS disease.

Rescue and evaluation of a recombinant PRRSV expressing porcine Interleukin-4

“…Previous studies demonstrated that pIL-4 markedly enhanced the protective immune response of pigs and improved the efficacy of the MLV in preventing PRRS disease [ 23 ], and pIL-4 can enhance immunogenicity of the PRRSV ORF5 gene vaccine [ 24 ]. Conversely, however, pigs that received PRRSV ORF7 DNA vaccine plus pIL-4-encoded plasmids did not develop any improved humoral and cellular immune responses [ 39 ].…”

“…In order to increase the efficacy of the vaccine, an alternative approach is to co-deliver cytokines to up-regulate the immune response of vaccine antigens. Interleukin-4 (IL-4) is a pleiotropic cytokine and has been used as an adjuvant to enhance immune response of PRRSV vaccines [ 23 , 24 ]. In addition, IL-4 may positively modulate vaccination mediated clearance of PRRSV [ 22 , 25 ].…”

Effect of porcine reproductive and respiratory syndrome (PRRS) modified-live virus (MLV) interventions on growth performance of infected growing pigs under field conditions

“…However, results from these experiments need to be interpret with caution in order to understand how natural virus infections can impact the performance of growing pig populations in the field. Field studies have shown that the wild-type virus exposure on growing pig populations is not homogeneous [32,33]. There was important variation in the frequency and in the timing of PRRSV detection in growing pigs raised in different barns at a single pig site [32].…”

“…Field studies have shown that the wild-type virus exposure on growing pig populations is not homogeneous [32,33]. There was important variation in the frequency and in the timing of PRRSV detection in growing pigs raised in different barns at a single pig site [32]. The timing of PRRSV detection in oral fluids samples collected over time from growing pigs on different pens of a single barn was also different [33].…”

“…It has been demonstrated that PRRS modified-live virus (MLV) vaccination with one full dose significantly reduces clinical consequences of PRRSV challenge compared to nonvaccinated pigs [19][20][21][22][23][24][25]. Aiming to further improve the protection against heterologous field viruses, researchers worldwide have developed new PRRSV immunization strategies [26][27][28][29][30][31][32][33][34].…”