Summary auto-generated
This study demonstrates that a genetically engineered pseudorabies virus (PRV) mutant lacking glycoproteins D and E (gD/gE-negative) can function as a safe, non-transmissible vaccine vector. The key innovation is that the mutant virus replicates locally through direct cell-to-cell transmission within vaccinated animals but produces non-infectious progeny virions lacking glycoprotein D, preventing transmission to contact animals. Researchers inserted the classical swine fever virus (CSFV) E2 envelope glycoprotein gene into this PRV mutant (strain ID57.1) and tested its protective efficacy in pigs. Following two vaccinations with ID57.1, pigs developed neutralizing antibodies against both PRV and CSFV. Upon viral challenge with virulent CSFV and PRV strains, vaccinated pigs showed no clinical disease signs, whereas unvaccinated controls developed severe illness. Virus shedding in vaccinated animals was reduced 100–1,000-fold compared to controls. The vaccine performed comparably to a transmissible vaccine strain (M205), though with slightly lower virus-neutralizing titers. This work establishes PRV gD/gE-negative mutants as biologically safe vaccine vectors capable of protecting against multiple viral diseases without risk of accidental transmission.
Key findings
- A non-transmissible PRV gD/gE-negative mutant expressing CSFV E2 glycoprotein protected vaccinated pigs against both Aujeszky's disease and classical swine fever
- The mutant vaccine virus spreads locally by cell-to-cell contact but produces non-infectious progeny virions incapable of transmission to unvaccinated animals
- Vaccinated pigs showed significant reduction in viral shedding (100–1,000-fold for CSFV challenge) and remained completely protected from clinical disease after lethal viral challenges
- The vaccine induced robust neutralizing antibody responses against both PRV and CSFV, with protective immunity lasting at least 76 days
- This self-restricted vaccine design eliminates transmission risk while maintaining the superior immunogenicity of live attenuated vaccines
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Abstract
Envelope glycoprotein D (gD) of pseudorabies virus (PRV) is essential for penetration but is not required for cell-to-cell spread. When animals are inoculated with a phenotypically complemented PRV gD mutant, the virus is able to spread locally by means of direct cell-to- cell transmission, but progeny virions released by infected cells are non-infectious because they lack gD. Therefore, the virus cannot be transmitted from inoculated animals to other animals. This property makes a PRV gD mutant an attractive candidate as a safe vaccine vector. To examine whether a self-restricted, non-transmissible PRV mutant can be used as a biologically safe vaccine vector, a gD/gE-negative PRV recombinant virus which expresses envelope glycoprotein E2 of classical swine fever virus was constructed. Vaccination of pigs showed that the recombinant virus was able to protect pigs against both Aujeszky's disease and classical swine fever.