Characteristics of the immune response of pigs to PRRS virusW. Meiera, J. Wheelerb, R.J. Husmanna, F. Osoriob and F.A. Zuckermanna
a Department of Veterinary Pathobiology, University of Illinois, Urbana, Illinois, USA
b Department of Veterinary and Biomedical Sciences, University of Nebraska, Lincoln, Nebraska, USA
Abstract - Several studies were conducted to evaluate the characteristics of the immunity induced by infection with wild type PRRS virus or vaccination with a PRRS modified live virus (MLV) vaccine. By monitoring the kinetics of the immune response to virus we made several remarkable observations. As a result of either infection with wild type PRRS virus or vaccination with a PRRS MLV vaccine, an antibody response was readily detectable by ELISA within 2 weeks after the administration of virus. A striking observation resulting from this research is that the generation of immunity able to mediate virus-inhibitory function, i.e., virus neutralizing antibodies and interferon gamma (IFN- )-producing T cells, becomes detectable only several weeks after exposure of pigs to either wild type virus or a MLV vaccine. The presence of virus-specific IFN- -producing cells was not frankly detectable until 8 to 10 weeks after virus administration. However, even then the frequency was fairly low as compared to the frequency of virus-specific cells induced by an Aujeszky's disease virus (ADV) MLV vaccine. In animals inoculated with the wild-type PRRS virus, the frequency of PRRS virus-specific IFN- -producing cells increased gradually over time so that by 9-10 months after infection it was comparable to the frequency induced by the administration of an ADV MLV vaccine within 2-3 weeks. By 12 months after infection with wild-type PRRS virus the titer of antibodies against this virus declines significantly, becoming even undetectable by ELISA in at least 30% of the pigs. In contrast, the intensity and quality of the virus-specific IFN- response increases in both quality and quantity. Of note was the observation that the IFN- ELISPOT remained at the same level in all animals infected with the wild-type virus from 300 to 690 days post infection (latest time tested). In contrast, during this time the presence of anti-PRRS virus antibodies in the serum of these animals decreased, so that at 690 days after infection 80% of the animals became negative by PRRSV IDEXX ELISA test. This is despite the fact that the frequency of IFN- -producing cells remained at the same level as that of the measurement at 300 days post infection. Although the reason for the delayed PRRS virus-inhibitory immune response is unclear at this time, we have evidence indicating that accessory cell-derived cytokines such as IL-12 and IL-10 are able to enhance and suppress, respectively, the intensity of the virus-specific cellular immune response at least in vitro. The complexity of the regulation of the immune response of pigs to PRRS virus is clearly indicated by the concomitant gradual decline of humoral immunity while the cell-mediated immunity increases. The rational development of effective PRRS virus vaccines requires an understanding of the mechanisms that regulate the kinetics, quality and intensity of the humoral and cellular immunity against this virus. Given the economic losses attributed to this disease this information is urgently needed. Based on these observations, it seems reasonable to postulate that an intrinsic property of PRRS virus is responsible for the inefficient stimulation of potentially protective immunity at least in the short term, namely, virus-neutralizing antibodies and IFN- -producing T cells. Although the reason(s) behind the poor immunogenicity of PRRS virus are unknown, we are currently examining several possibilities. We believe that clarification of this issue is essential for the development and formulation of a highly immunogenic and effective PRRS vaccine.
Corresponding author: F.A. Zuckermanna Tel.: (1) 217 333 7767; fax: (1) 217 333 7421;
© INRA, EDP Sciences 2000