Skip to main content

Varicella zoster virus vaccines: potential complications and possible improvements

Abstract

Varicella zoster virus (VZV) is the causative agent of varicella (chicken pox) and herpes zoster (shingles). After primary infection, the virus remains latent in sensory ganglia, and reactivates upon weakening of the cellular immune system due to various conditions, erupting from sensory neurons and infecting the corresponding skin tissue. The current varicella vaccine (v-Oka) is highly attenuated in the skin, yet retains its neurovirulence and may reactivate and damage sensory neurons. The reactivation is sometimes associated with postherpetic neuralgia (PHN), a severe pain along the affected sensory nerves that can linger for years, even after the herpetic rash resolves. In addition to the older population that develops a secondary infection resulting in herpes zoster, childhood breakthrough herpes zoster affects a small population of vaccinated children. There is a great need for a neuro-attenuated vaccine that would prevent not only the varicella manifestation, but, more importantly, any establishment of latency, and therefore herpes zoster. The development of a genetically-defined live-attenuated VZV vaccine that prevents neuronal and latent infection, in addition to primary varicella, is imperative for eventual eradication of VZV, and, if fully understood, has vast implications for many related herpesviruses and other viruses with similar pathogenic mechanisms.

This is a preview of subscription content, access via your institution.

References

  1. Abendroth A, Arvin A. 1999. Varicella-zoster virus immune evasion. Immunological reviews, 168: 143–156.

    PubMed  Article  CAS  Google Scholar 

  2. Arvin A M. 1995. Aspects of the host response to varicella-zoster virus: a review of recent observations. Neurology, 45: S36–37.

    PubMed  Article  CAS  Google Scholar 

  3. Arvin A M. 2001. Varicella-zoster virus: molecular virology and virus-host interactions. Curr Opin Microbiol, 4: 442–449.

    PubMed  Article  CAS  Google Scholar 

  4. Chesnut G, McClain D, Galeckas K. 2012. Varicella-zoster virus in children immunized with the varicella vaccine. Cutis, 90: 114–116.

    PubMed  Google Scholar 

  5. Choo P W, Donahue J G, Manson J E, Platt R. 1995. The epide-miology of varicella and its complications. J Infect Dis, 172: 706–712.

    PubMed  Article  CAS  Google Scholar 

  6. Cohen J I, Seidel K E. 1993. Generation of varicella-zoster virus (VZV) and viral mutants from cosmid DNAs: VZV thymidylate synthetase is not essential for replication in vitro. Proc Natl Acad Sci U S A, 90: 7376–7380.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  7. Cole N L, Grose C. 2003. Membrane fusion mediated by herpesvirus glycoproteins: the paradigm of varicella-zoster virus. Rev Med Virol, 13: 207–222.

    PubMed  Article  CAS  Google Scholar 

  8. Collaco A M, Rahman S, Dougherty E J, Williams B B, Geusz M E. 2005. Circadian regulation of a viral gene promoter in live transgenic mice expressing firefly luciferase. Mol Imaging Biol, 7: 342–350.

    PubMed  Article  Google Scholar 

  9. Contag C H, Bachmann M H. 2002. Advances in in vivo bioluminescence imaging of gene expression. Annu Rev Biomed Eng, 4: 235–260.

    PubMed  Article  CAS  Google Scholar 

  10. Contag C H, Spilman S D, Contag P R, Oshiro M, Eames B, Dennery P, Stevenson D K, Benaron D A. 1997. Visualizing gene expression in living mammals using a bioluminescent reporter. Photochem Photobiol, 66: 523–531.

    PubMed  Article  CAS  Google Scholar 

  11. Doyle T C, Burns S M, Contag C H. 2004. In vivo bioluminescence imaging for integrated studies of infection. Cell Microbiol, 6: 303–317.

    PubMed  Article  CAS  Google Scholar 

  12. Drolet M, Brisson M, Schmader K E, Levin M J, Johnson R, Oxman M N, Patrick D, Blanchette C, Mansi J A. 2010. The impact of herpes zoster and postherpetic neuralgia on healthrelated quality of life: a prospective study. CMAJ: Canadian Medical Association journal = journal de l’Association medicale canadienne, 182: 1731–1736.

    Article  Google Scholar 

  13. Dulal K, Zhang Z, Zhu H. 2009. Development of a gene capture method to rescue a large deletion mutant of human cytomegalovirus. Journal of Virological Methods, 157: 180–187.

    PubMed  Article  CAS  Google Scholar 

  14. Dulal K, Silver B, Zhu H. 2012. Use of Recombination-Mediated Genetic Engineering for Construction of Rescue Human Cytomegalovirus Bacterial Artificial Chromosome Clones. Biomed and Biotechnol.

    Google Scholar 

  15. Fan S, Maguire C A, Ramirez S H, Bradel-Tretheway B, Sapinoro R, Sui Z, Chakraborty-Sett S, Dewhurst S. 2005. Valproic acid enhances gene expression from viral gene transfer vectors. J Virol Methods, 125: 23–33.

    PubMed  Article  CAS  Google Scholar 

  16. Gershon M D, Gershon A A. 2010. VZV infection of keratinocytes: production of cell-free infectious virions in vivo. Curr Top Microbiol Immunol, 342: 173–188.

    PubMed  CAS  Google Scholar 

  17. Gilden D H, Kleinschmidt-DeMasters B K, LaGuardia J J, Mahalingam R, Cohrs R J. 2000. Neurologic complications of the reactivation of varicella-zoster virus. N Engl J Med, 342: 635–645.

    PubMed  Article  CAS  Google Scholar 

  18. Harnisch J P. 1984. Zoster in the elderly: clinical, immunologic and therapeutic considerations. J Am Geriatr Soc, 32: 789–793.

    PubMed  CAS  Google Scholar 

  19. Hastings J W. 1983. Biological diversity, chemical mechanisms, and the evolutionary origins of bioluminescent systems. J Mol Evol, 19: 309–321.

    PubMed  Article  CAS  Google Scholar 

  20. Hatchette T, Tipples G A, Peters G, Alsuwaidi A, Zhou J, Mailman T L. 2008. Foscarnet salvage therapy for acyclovir-resistant varicella zoster: report of a novel thymidine kinase mutation and review of the literature. Pediatr Infect Dis J, 27: 75–77.

    PubMed  Article  Google Scholar 

  21. Kimberlin D W, Whitley R J. 2007. Varicella-zoster vaccine for the prevention of herpes zoster. N Engl J Med, 356: 1338–1343.

    PubMed  Article  CAS  Google Scholar 

  22. Klassen T P, Hartling L, Wiebe N, Belseck E M. 2005. Acyclovir for treating varicella in otherwise healthy children and adolescents. Cochrane Database Syst Rev: CD002980.

    Google Scholar 

  23. Kurfurst M, Ghisla S, Hastings J W. 1983. Bioluminescence emission from the reaction of luciferase-flavin mononucleotide radical with O2. Biochemistry, 22: 1521–1525.

    PubMed  Article  CAS  Google Scholar 

  24. Leung J, Harpaz R, Molinari N A, Jumaan A, Zhou F. 2011. Herpes zoster incidence among insured persons in the United States, 1993–2006: evaluation of impact of varicella vaccination. Clin Infect Dis, 52: 332–340.

    PubMed  Article  Google Scholar 

  25. Liesegang T J. 2004. Herpes zoster virus infection. Curr Opin Ophthalmol, 15: 531–536.

    PubMed  Article  Google Scholar 

  26. Lydick E, Epstein R S, Himmelberger D, White C J. 1995. Herpes zoster and quality of life: a self-limited disease with severe impact. Neurology, 45: S52–53.

    PubMed  Article  CAS  Google Scholar 

  27. Nagaike K, Mori Y, Gomi Y, Yoshii H, Takahashi M, Wagner M, Koszinowski U, Yamanishi K. 2004. Cloning of the varicellazoster virus genome as an infectious bacterial artificial chromosome in Escherichia coli. Vaccine, 22: 4069–4074.

    PubMed  Article  CAS  Google Scholar 

  28. Niizuma T, Zerboni L, Sommer M H, Ito H, Hinchliffe S, Arvin A M. 2003. Construction of varicella-zoster virus recombinants from parent Oka cosmids and demonstration that ORF65 protein is dispensable for infection of human skin and T cells in the SCID-hu mouse model. J Virol, 77: 6062–6065.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  29. Opstelten W, Mauritz J W, de Wit N J, van Wijck A J, Stalman W A, van Essen G A. 2002. Herpes zoster and postherpetic neuralgia: incidence and risk indicators using a general practice research database. Fam Pract, 19: 471–475.

    PubMed  Article  Google Scholar 

  30. Rehemtulla A, Stegman L D, Cardozo S J, Gupta S, Hall D E, Contag C H, Ross B D. 2000. Rapid and quantitative assessment of cancer treatment response using in vivo bioluminescence imaging. Neoplasia, 2: 491–495.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  31. Reichelt M, Zerboni L, Arvin A M. 2008. Mechanisms of varicellazoster virus neuropathogenesis in human dorsal root ganglia. J Virol, 82: 3971–3983.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  32. Saksena M M, Wakisaka H, Tijono B, Boadle R A, Rixon F, Takahashi H, Cunningham A L. 2006. Herpes simplex virus type 1 accumulation, envelopment, and exit in growth cones and varicosities in mid-distal regions of axons. J Virol, 80: 3592–3606.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  33. Uebe B, Sauerbrei A, Burdach S, Horneff G. 2002. Herpes zoster by reactivated vaccine varicella zoster virus in a healthy child. Eur J Pediatr, 161: 442–444.

    PubMed  Article  Google Scholar 

  34. Vazquez M. 2004. Varicella zoster virus infections in children after the introduction of live attenuated varicella vaccine. Curr Opin Pediatr, 16: 80–84.

    PubMed  Article  Google Scholar 

  35. Warden C, Tang Q, Zhu H. 2011. Herpesvirus BACs: past, present, and future. J Biomed Biotechnol, 2011: 124595.

    PubMed  Article  PubMed Central  Google Scholar 

  36. Warming S, Costantino N, Court D L, Jenkins N A, Copeland N G. 2005. Simple and highly efficient BAC recombineering using galK selection. Nucleic Acids Res, 33: e36.

    PubMed  Article  PubMed Central  Google Scholar 

  37. White M R, Masuko M, Amet L, Elliott G, Braddock M, Kingsman A J, Kingsman S M. 1995. Real-time analysis of the transcriptional regulation of HIV and hCMV promoters in single mammalian cells. J Cell Sci, 108( Pt 2): 441–455.

    PubMed  CAS  Google Scholar 

  38. Whitley R J. 2005. Changing dynamics of varicella-zoster virus infections in the 21st century: the impact of vaccination. J Infect Dis, 191: 1999–2001.

    PubMed  Article  Google Scholar 

  39. Yih W K, Brooks D R, Lett S M, Jumaan A O, Zhang Z, Clements K M, Seward J F. 2005. The incidence of varicella and herpes zoster in Massachusetts as measured by the Behavioral Risk Factor Surveillance System (BRFSS) during a period of increasing varicella vaccine coverage, 1998–2003. BMC Public Health, 5: 68.

    PubMed  Article  PubMed Central  Google Scholar 

  40. Zerboni L, Arvin A. 2011. Investigation of varicella-zoster virus neurotropism and neurovirulence using SCID mouse-human DRG xenografts. J Neurovirol, 17: 570–577.

    PubMed  Article  CAS  Google Scholar 

  41. Zerboni L, Reichelt M, Arvin A. 2010. Varicella-zoster virus neurotropism in SCID mouse-human dorsal root ganglia xenografts. Curr Top Microbiol Immunol, 342: 255–276.

    PubMed  CAS  Google Scholar 

  42. Zhang Y, Muyrers J P, Testa G, Stewart A F. 2000. DNA cloning by homologous recombination in Escherichia coli. Nat Biotechnol, 18: 1314–1317.

    PubMed  Article  CAS  Google Scholar 

  43. Zhang Z, Huang Y, Zhu H. 2008. A highly efficient protocol of generating and analyzing VZV ORF deletion mutants based on a newly developed luciferase VZV BAC system. J Virol Methods, 148: 197–204.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  44. Zhang Z, Rowe J, Wang W, Sommer M, Arvin A, Moffat J, Zhu H. 2007. Genetic analysis of varicella-zoster virus ORF0 to ORF4 by use of a novel luciferase bacterial artificial chromosome system. J Virol, 81: 9024–9033.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  45. Zhang Z, Selariu A, Warden C, Huang G, Huang Y, Zaccheus O, Cheng T, Xia N, Zhu H. 2010. Genome-wide mutagenesis reveals that ORF7 is a novel VZV skin-tropic factor. PLoS pathogens, 6: e1000971.

    PubMed  Article  PubMed Central  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Hua Zhu.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Silver, B., Zhu, H. Varicella zoster virus vaccines: potential complications and possible improvements. Virol. Sin. 29, 265–273 (2014). https://doi.org/10.1007/s12250-014-3516-9

Download citation

Keywords

  • varicella zoster virus
  • herpesvirus
  • vaccine
  • neurovirulence
  • neuro-attenuation
  • latency
  • latent infection
  • herpes zoster
  • shingles
  • chicken pox
  • ORF7