Summary auto-generated
Researchers tested DNA vaccination against Aujeszky's disease (pseudorabies virus infection) in pigs, the natural host animal. Plasmid DNA vectors expressing either glycoprotein C (gC) or glycoprotein D (gD) of pseudorabies virus were injected into piglets via intramuscular or intradermal routes. Pigs vaccinated with the gC expression plasmid developed serum antibodies with neutralizing activity against the virus and mounted a detectable cellular immune response. When challenged with lethal pseudorabies virus strains, gC-vaccinated animals showed complete protection against the moderately virulent 75V19 strain and partial protection against the highly virulent NIA-3 strain. In contrast, gD vaccination provided no protection. As little as 1-10 micrograms of gC plasmid DNA per dose induced partial protection, while higher doses ensured broader immunity. Specific antibodies persisted for at least 9 months post-vaccination. The gD-vaccinated and control animals died from challenge infection. This study demonstrates that DNA vaccination can effectively protect large animals against lethal viral disease, offering a safer alternative to traditional inactivated vaccines.
Key findings
- DNA vaccination with plasmid encoding pseudorabies virus glycoprotein C (gC) provided complete protection against lethal challenge with PrV strain 75V19 and partial protection against highly virulent NIA-3 strain in pigs
- gC vaccination induced both humoral antibodies with neutralizing activity and cellular immune responses, detectable for at least 9 months after vaccination
- Minimal effective dose was 1-10 micrograms of gC plasmid DNA delivered via intramuscular or intradermal injection
- Glycoprotein D (gD) vaccination failed to protect animals against lethal challenge, distinguishing it from gC as an effective vaccine antigen
- This represents the first demonstration of DNA vaccination protecting a large animal species against lethal viral disease, with protection comparable to or exceeding conventional inactivated vaccines
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Abstract
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.