title: Non-transmissible pseudorabies virus gp50 mutants: a new generation of safe live vaccines.
abstract: Envelope glycoprotein gp50 of pseudorabies virus (PRV) is essential for virus entry, but is not required for subsequent steps in the viral replication cycle. Phenotypically-complemented gp50 null mutants can infect cells and can spread, both in vitro and in vivo, by direct cell-to-cell transmission. However, progeny virions released by the infected cells are non-infectious because they lack gp50. Therefore, these viruses cannot be transmitted from infected animals to contact animals. These properties could make PRV gp50 null mutants attractive candidates as safe non-transmissible live vaccines. To establish whether phenotypically-complemented PRV gp50 null mutants and gp50 + gp63 double mutants could be used as live vaccines against Aujeszky's disease, the virulence and immunogenicity of these mutants were tested in pigs. Our results show that a gp50 null mutant has a greatly reduced virulence for pigs, and that pigs immunized with such a mutant were protected from clinical signs of Aujeszky's disease after a challenge inoculation with the virulent wild-type PRV strain NIA-3. PRV gp50 + gp63 deletion mutants proved to be non-virulent for pigs and were somewhat less immunogenic, since immunized animals showed some fever and growth retardation after challenge inoculation. Replication of wild-type challenge virus was significantly reduced, but could not completely be prevented, in pigs immunized with a gp50 null mutant, and was reduced less in pigs immunized with a gp50 + gp63 deletion mutant. Furthermore, infectious virus could not be recovered from oropharyngeal fluid or tissues from pigs inoculated with a gp50 null mutant or a gp50 + gp63 deletion mutant.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Virology, Central Veterinary Institute, Lelystad, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Peeters
authors.forename: A
authors.initials: A
authors.lastname: Bouma
authors.forename: T
authors.initials: T
authors.lastname: de Bruin
authors.forename: R
authors.initials: R
authors.lastname: Moormann
authors.forename: A
authors.initials: A
authors.lastname: Gielkens
authors.forename: T
authors.initials: T
authors.lastname: Kimman
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002460:Cell Line; D011558:Herpesvirus 1, Suid / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D008213:Lymphocyte Activation; D009154:Mutation; D009500:Neutralization Tests / Q000662:veterinary; D011557:Pseudorabies / Q000517:prevention & control; D013552:Swine; D013553:Swine Diseases / Q000517:prevention & control; D014613:Vaccines, Attenuated / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C042966:pseudorabies virus glycoproteins