Vaccination with DNA constructs encoding viral antigens has been shown to induce antiviral immunity in various model hosts. However, relevant natural virus-host systems have so far been analysed to only a very limited extent. To test the efficacy of DNA vaccination in an economically important large animal, pigs were immunized against Aujeszky's disease, a serious virus infection caused by the alphaherpesvirus pseudorabies virus (PrV), which is characterized by severe central nervous and respiratory symptoms. After vaccination with plasmid vectors containing genes for immunogenic envelope glycoproteins C or D (gC or gD) of PrV under control of the major immediate early promotor of human cytomegalovirus, animals developed serum antibodies which recognized the respective antigen in immunoblot and exhibited neutralizing activity. Animals vaccinated with the gC expression plasmid were fully protected against a lethal challenge with PrV strain 75V19, and showed partial protection against the highly virulent NIA-3 strain. In contrast, protection was not observed after vaccination with the gD plasmid. Three intramuscular or intradermal immunizations with as little as 1 microgram of gC plasmid DNA resulted in sero-conversion and partial protection against lethal NIA-3 Infection. Specific antibodies were detected until at least 9 months after vaccination. In addition, a cellular immune response specific for gC could be demonstrated in proliferation assays of peripheral mononuclear lymphocytes. Our results thus demonstrate the potency of DNA vaccination for protection of large animals against a lethal virus infection.


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