Mechanisms of protective immunity against Aujeszky's disease virus

Abstract - An understanding of the role that different types of immune effector mechanisms have in mediating protective immunity against virus diseases of swine is key to the development of effective vaccines for this species. The abundant literature available on the efficacy of vaccines against Aujeszky's disease virus (ADV) has provided evidence that inactivated ADV vaccines are not as effective as modified live virus (MLV) vaccines at stimulating protective immunity. The fact that similar titers of virus-neutralizing antibodies are present in pigs receiving either type of vaccine has fueled the speculation that cell-mediated immunity must therefore be responsible for mediating protection from disease. Certainly, the lesser ability of inactivated ADV vaccines to provide protective immunity must reflect the inability of this type of vaccine to induce sufficient levels of immune effector mechanism(s) important for protection. However, the exact nature of this deficit is unknown. We have examined this issue by measuring the serum titer of virus-neutralizing antibodies and the frequency of ADV-specific interferon-gamma (IFN- )-producing cells in the peripheral blood mononuclear cells of pigs after immunization with either inactivated or MLV ADV vaccines. We found that while both MLV and inactivated vaccines are able to induce similar levels of neutralizing antibodies, an inactivated vaccine is not as effective as a MLV vaccine at stimulating ADV-specific IFN- -producing cells. Indeed we found a correlation between the intensity of this response and the level of protective immunity. This correlation was further confirmed by the observation that pigs immunized with inactivated virus in combination with either human recombinant IL-12 or an oil-in-water adjuvant, develop an enhanced IFN- response and level of protective immunity, as compared to pigs receiving the inactivated virus alone. In contrast, the titer of virus neutralizing antibodies produced in response to the inactivated vaccine was mildly affected by either of these adjuvants. The data obtained clearly show that there are differences in the quality and quantity of the immunity induced by a live versus an inactivated ADV vaccine. While inactivated commercial vaccines are equally efficient as a MLV vaccine at inducing humoral immunity, they only induce a weak and transient virus-specific IFN- response. In contrast, a MLV vaccine induces a robust virus-specific IFN- response. In all of the different ADV vaccine formulations tested in our experiments, a high level of protective immunity correlated with the presence of a strong IFN- response, while the titer of virus-neutralizing antibodies did not. Although the results from this study do not rule out a role for humoral immunity in protection, they do suggest that cell-mediated immunity participate in providing a high degree of protective immunity. The data presented argue in favor of the notion that the level of cell-mediated immunity is a major factor in determining the level of protection from ADV-induced disease. At the very minimum, a strong IFN- response in a pig is a good predictor that the animal has developed a strong protective immune response against this virus.