NON-TRANSMISSIBLE PSEUDORABIES VIRUS GP50 MUTANTS - A NEW-GENERATION OF SAFE LIVE VACCINES

Envelope glycoprotein gp50 of pseudorabies virus (PRV) is essential fo r virus entry, but is not required for subsequent steps in the viral r eplication cycle. Phenotypically-complemented gp50 null mutants can in fect cells and can spread, both in vitro and in vivo, by direct cell-t o-cell transmission. However, progeny virions released by the infected cells are non-infectious because they lack gp50. Therefore, these vir uses cannot be transmitted from infected animals to contact animals. T hese properties could make PRV gp50 null mutants attractive candidates as safe non-transmissible live vaccines. To establish whether phenoty pically-complemented PRV gp50 null mu tan ts and gp50 + gp63 double mu tants could be used as live vaccines against Aujeszky's disease, the v irulence and immunogenicity of these mutants were tested in pigs. Our results show that a gp50 null mutant has a greatly reduced virulence f or pigs, and that pigs immunized with such a mutant were protected fro m clinical signs of Aujeszky's disease after a challenge inoculation w ith the virulent wild-type PRV strain NIA-3. PRV gp50 + gp63 deletion mutants proved to be non-virulent for pigs and were somewhat less immu nogenic, since immunized animals showed some fever and growth retardat ion after challenge inoculation. Replication of wild-type challenge vi rus was significantly reduced, but could not completely be prevented, in pigs immunized with a gp50 null mutant, and was reduced less in pig s immunized with a gp50 + gp63 deletion mutant. Furthermore, infectiou s virus could not be recovered from oropharyngeal fluid or tissues fro m pigs inoculated with a gp50 null mutant or a gp50 + gp63 deletion mu tant. These results indicate that PRV gp50 null mutants and gp50 + gp6 3 deletion mutants may be used as safe non-transmissible live vaccines against Aujeszky's disease, or as safe carrier vaccines for the deliv ery of heterologous gene products.