. . . . • masque Genetic differences between VZV wild-type and Oka strains Judith Breuer Professor of Virology St Barts and The London Hospital Medical School UK 1 Rome, Italy - March 18, 2005
Oka vaccine Live attentuated virus
Bang BAN7 B A C Bang + J 95 Reproduced from Barrett-Muir W, et al.J Virol 2002;76:1971-9with permission from the American Society for Microbiology
E M Bang BAN7 Bang + J 95 Loparev VN, et al. J Virol 2004;78: 8349-58.
E A Bang BAN7 Bang + 95 Grose, J clin Virol 2005; in press
Evidence that ORF 47 p may be a virulence factor Reduced ability of vOka to spread from T-cells to melanoma cell lines (Soong et al, 2000) Similar to ORF 47 mutant Soong W, et al. J Virol. 2000;74:1864-70.
Fig. 1. Gel electrophoresis of polymerase chain reaction (PCR) products. A: Amplification across BssHII site in ORF 62 and restriction enzyme digest. Lane 1: Parental Oka virus; lane 2, UK wild type J virus; lane 3, Oka Merck vaccine; lanes 4–6, vaccine zoster viruses;lanes 7–18, vaccine rash viruses; lane 19, molecular weight marker (band sizes 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9 kb).B: Amplification across Alu1 site in ORF 6 and restriction digest. Lane 1: 100 bp molecular weight marker; lane 2, parental Oka virus; lane 3, UK wild type J virus; lane 4, Oka Merck vaccine; lanes 5–7, vaccine zoster viruses; lanes 8–19, vaccine rash viruses; lane 20, 100 bp molecular weight marker.
Vaccine preparations in comparison to pOka Is IE62 necessary for attenuation ?
Does the vaccine protect against wild type viruses? IE 62 . Overlapping peptide pools CD8 + cells assayed by Ifn staining Peptide pool 5 recognised by A2 restricted PBLs
Conclusion • wtVZV varies geographically, and between related strains • vOka vaccine is attenuated biologically and clinically • The vOka vaccine is made up of a mixture of strains • Attenuation is likely to be multigenic and involve ORFs 30-54 • vOka immune protection may be enhanced by the mixture of wt and vaccine mutations in the vaccine preparation.