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Genetic differences between VZV wild-type and Oka strains Judith Breuer Professor of Virology

. 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.

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Genetic differences between VZV wild-type and Oka strains Judith Breuer Professor of Virology

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  1. . . . . • 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

  2. Oka vaccine Live attentuated virus

  3. 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

  4. E M Bang BAN7 Bang + J 95 Loparev VN, et al. J Virol 2004;78: 8349-58.

  5. E A Bang BAN7 Bang + 95 Grose, J clin Virol 2005; in press

  6. Which are the genetic correlates of vaccine attenuation?

  7. 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.

  8. Vaccine preparations in comparison to pOka

  9. Vaccine preparations in comparison to pOka

  10. Vaccine preparations in comparison to pOka

  11. Vaccine preparations in comparison to pOka

  12. 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.

  13. Which mutations are important for attenuation?

  14. Vaccine preparations in comparison to pOka Is IE62 necessary for attenuation ?

  15. 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

  16. 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.

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