INTERLEUKIN-12 ENHANCES THE VIRUS-SPECIFIC INTERFERON-GAMMA RESPONSE OF PIGS TO AN INACTIVATED PSEUDORABIES VIRUS-VACCINE

Cell-mediated immunity is a major component of the host defense system against viral infections. Since interleukin (IL)-12 has been shown to be a potent stimulus for the in vivo generation of interferon-gamma ( IFN-gamma)-producing T cells (i.e. Th-1 cells) in laboratory animals, we evaluated the effect of IL-12 on the cellular immune response of pi gs to vaccination against pseudorabies virus (PrV), a herpesvirus of s wine. The magnitude of the cellular immune response was measured by IF N-gamma ELISPOT analysis of peripheral blond mononuclear cells (PBMC) from pigs which had been immunized twice, at 2-week intervals, with ei ther, modified live virus (MLV) alone or with a commercial inactivated PrV vaccine with or without the coadministration of human recombinant IL-12 (HrIL-12). No significant differences in the titer of virus-neu tralizing antibodies or in the intensity of the virus-specific lymphop roliferative response among the different treatment groups was observe d. However, the number of virus-specific IFN-gamma-producing cells amo ng PBMC isolated from animals receiving the MLV vaccine was on average 3.5 times more than animals immunized with the inactivated vaccine (P = 0.01). Administration of the inactivated vaccine and IL-12 induced a two-fold higher frequency of virus-specific IFN-gamma-producing cell s from that induced by the inactivated vaccine alone(P < 0.05). Despit e this enhancement, the level of protection from lethal PrV challenge provided by the inactivated vaccine in combination with IL-12 was the same as that induced by the inactivated vaccine alone. Both of these v accination regimes provided significantly lower levels of protection t han those afforded by the MLV vaccine. This study demonstrates that an inactivated PrV vaccine is a poor inducer of virus-specific IFN-gamma -producing cells and that this response can be enhanced by administrat ion of exogenous IL-12. The data provides evidence of a dichotomy in t he humoral and cellular immune responses of pigs to a viral antigen an d implies the existence of a Th-1/Th-2 type regulation of the anti-vir al immune response in pigs. (C) 1998 Elsevier Science B.V. All rights reserved.