title: Vaccination with an attenuated Creutzfeldt-Jakob disease strain prevents expression of a virulent agent.
abstract: Although slow and persistent viruses often escape host defenses infection may be prevented by live vaccines. To determine whether an attenuated "slow" strain of the Creutzfeldt-Jakob disease agent (SY) could block expression of a virulent "fast" strain (FU), outbred CD-1 mice were inoculated intracerebrally with low infectious doses of SY and challenged 80 days later with higher doses of FU. For comparison, the same SY and FU samples were inoculated in two parallel control groups. All 18 superinfected mice showed incubation times identical to those inoculated with only the SY strain, yielding clinical disease >110 days later than predicted for the FU strain. Neurological signs, such as scratching and an extended clinical phase, were also characteristic for SY but not FU infection. Moreover, the widespread cortical pathology of FU was not detectable in superinfected mice. Western blot analyses further showed no strain-specific differences in prion protein (PrP) band profiles for all experimental groups, although there was approximately 10-fold more protease-resistant PrP (PrP-res) in FU brains during terminal disease. In contrast, infectivity assays revealed an approximately 10,000-fold difference between SY and FU at terminal stages, indicating that PrP-res content does not correlate with infectivity. In summary, an attenuated strain of the Creutzfeldt-Jakob disease agent evokes substantial interference against a virulent agent. Because superinfected mice had little PrP-res just before the onset of clinical disease and retained abundant cellular PrP, cellular PrP was not the factor limiting FU replication. The mechanisms underlying SY interference are not understood but could be based on host recognition of foreign molecular features shared by this class of invasive agents involving antibody production, and possibly involve defective viral particles produced by attenuated variants.
authors.affiliation: Section of Neuropathology, Yale Medical School, 310 Cedar Street, New Haven, CT 06510, USA. laura.manuelidis@yale.edu
authors.forename: L
authors.initials: L
authors.lastname: Manuelidis
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000473:pathology; D007562:Creutzfeldt-Jakob Syndrome / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control; D051379:Mice; D011328:Prions / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D013997:Time Factors; D014612:Vaccines; D014774:Virulence
chemical_list: D011328:Prions; D014612:Vaccines