Date Full Report Received


Date Abstract Report Received



Primary Investigator:

Interferon (IFN)-alpha is the most important anti-viral substance produced by mammalian cells in response to a viral infection. Accordingly, the production of IFN-alpha by an animal during a viral infection is known to be a principal determinant of the animal’s ability to fight the infection. In addition, this substance is known to play a major role in regulating and promoting the development of vaccine induced anti-viral immunity and can act as a vaccine adjuvant. Previous studies have indicated that one characteristic of porcine reproductive and respiratory syndrome (PRRS) virus is the failure to stimulate an IFN-alpha response. During our investigations we have determined that a common attribute of PRRS virus isolates, including strains of PRRS virus that have been utilized to prepare the modified live virus (MLV) vaccines, have the ability to suppress the IFN-alpha response of pig leukocytes to other types of pig viruses that otherwise stimulate a strong IFN-alpha response. Thus, the goal of this project was determine the influence of the IFN-alpha inhibitory property of attenuated PRRS virus strains on their ability to stimulate protective immunity. The main impetus for this goal is the apparent lack of potency of currently available vaccines against PRRS virus, which primarily apparently can only provide protection against an infection by a very closely related PRRS virus. The trust to test our notion was further supported by the observation that IFN-alpha can act as a vaccine adjuvant for PRRS modified live virus vaccine as demonstrated by its ability to enhance the cellular immune response of pigs to this veterinary biologic (Meier et al., 2004). Our hypothesis is that the IFN-alpha-suppressing property of a PRRS virus vaccine renders it unable to stimulate strong protective immunity, leading to their suboptimal performance. To test this hypothesis, we examined the vaccine potency several attenuated PRRS virus strains, which either had a marked, mild or negligible ability to inhibit the ability of porcine leukocytes to produce IFN-alpha. Two vaccination and challenge studies were conducted with groups of 8-10 week-old pigs, which were immunized with the different PRRS virus vaccine strains. Two additional groups of pigs for each experiment were not vaccinated and served as controls. Four weeks later, one of the unvaccinated groups and all of the vaccinated groups were challenged with the highly virulent atypical PRRS virus isolate NADC-20. At 7-10 days after the virus challenge the amount of virus in the bronchoalveolar lavage fluid and weight change were measured in all groups and used as parameters to evaluate protective immunity. The results obtained in both experiments demonstrated that as predicted, the PRRS live attenuated virus vaccine exhibiting minimal IFN-alpha suppressing activity was the most effective in providing protection from the clinical signs resulting from the challenge with a genetically divergent and highly virulent PRRS virus. This was evidenced by a significantly higher (35-100%) body weight gain during the seven days after the virus challenge, as compared to that of the pigs immunized with vaccine viruses that have either a mild or strong IFN-alpha inhibitory effect. In addition, the virus load in the lung was significantly reduced or eliminated in the pigs that were immunized with the virus with the minimal IFN-alpha suppressing activity. The results of this project indicate that the level of IFN-alpha inhibitory effect of a PRRS MLV vaccine on porcine leukocytes can be used as a predictive parameter of the potential effectiveness (potency) of PRRS virus vaccine and that the use of this biological property of this virus as selection criteria for vaccine strain selection will aid in the development of a more effective PRRS virus vaccine.
Contact information: Federico Zuckermann, University of Illinois, College of Veterinary Medicine. Email: fazaaa@illinois.edu.