Varicella and Zoster

  • Anne A. Gershon


It has been more than 30 years since Michiaki Takahashi of Osaka, Japan, attenuated the varicella–zoster virus (VZV) to produce the Oka vaccine strain of live, attenuated varicella vaccine. The initial trials of safety, immunogenicity, and efficacy were carried out in Japan in the early 1970s. Subsequently, large-scale confirmatory studies of immunogenicity and safety were performed mainly in the United States. Initially, these involved immunocompromised children, but later healthy children were immunized, and there was greater interest in vaccinating healthy populations than immunocompromised ones. These clinical trials culminated in the licensure of a single dose of varicella vaccine for all American children in 1995. Currently, the vaccine is used to prevent chickenpox worldwide and has been licensed for universal vaccination in many countries including Australia, Canada, Germany, Israel, Qatar, Sicily, South Korea, Taiwan, and Uruguay (Gershon et al. 2008). While it has not achieved general acceptance in Japan, interest in its use there is increasing. While it took many years to gain general acceptance in Japan, the vaccine is now being used more and more in that country. The latest exciting advance regarding the Oka vaccine is that a high-titered formulation is now being used as a therapeutic vaccine to boost immunity to VZV in the elderly with latent infection in order to prevent zoster. This chapter discusses the almost 40-year saga of the development of vaccines against VZV.


Varicella Vaccine Varicella Vaccination Immunocompromised Child Vaccine Failure Human Embryonic Lung Fibroblast 
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  1. Arbeter AL, Granowetter S, Starr B et al (1990) Immunization of children with acute lymphoblastic leukemia with live attenuated varicella vaccine without complete suspension of chemotherapy. Pediatrics 85:338–344PubMedGoogle Scholar
  2. Arvin A, Gershon A (2006) Control of varicella: why is a two-dose schedule necessary? Pediatr Infect Dis J 25:475–476CrossRefPubMedGoogle Scholar
  3. Asano Y, Nakayama H, Yazaki T et al (1977) Protection against varicella in family contacts by immediate inoculation with live varicella vaccine. Pediatrics 59:3–7PubMedGoogle Scholar
  4. Brisson M, Edmunds WJ, Law B et al (2001) Epidemiology of varicella zoster virus infection in Canada and the United Kingdom. Epidemiol Infect 127:305–314CrossRefPubMedGoogle Scholar
  5. Broyer M, Tete MT, Guest G et al (1997) Varicella and zoster in children after kidney transplantation: Long term results of vaccination. Pediatrics 99:35–39CrossRefPubMedGoogle Scholar
  6. Brunell PA, Shehab Z, Geiser C et al (1982) Administration of live varicella vaccine to children with leukemia. Lancet 2:1069–1073CrossRefPubMedGoogle Scholar
  7. Brunell PA, Taylor-Wiedeman J, Geiser CF et al (1986) Risk of herpes zoster in children with leukemia: Varicella vaccine compared with history of chickenpox. Pediatrics 77:53–56PubMedGoogle Scholar
  8. Centers for Disease Control (1996) Prevention of varicella: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 45:1–36Google Scholar
  9. Chaves SS, Gargiullo P, Zhang JX et al (2007) Loss of vaccine-induced immunity to varicella over time. N Engl J Med 356:1121–1129CrossRefPubMedGoogle Scholar
  10. Chen J, Gershon A, Silverstein SJ et al (2003). Latent and lytic infection of isolated guinea pig enteric and dorsal root ganglia by varicella zoster virus. J Med Virol 70:S71–S78CrossRefPubMedGoogle Scholar
  11. Chen JJ, Zhu Z, Gershon AA et al (2004) Mannose 6-phosphate receptor dependence of varicella zoster virus infection in vitro and in the epidermis during varicella and zoster. Cell 119:915–926CrossRefPubMedGoogle Scholar
  12. Civen R, Lopez AS, Zhang J et al (2008). Varicella outbreak epidemiology in an active surveillance site, 1995–2005. J Infect Dis 197(Suppl 2):S114–S119CrossRefPubMedGoogle Scholar
  13. Committee on Infectious Diseases (1995) Live attenuated varicella vaccine. Pediatrics 95:791–796Google Scholar
  14. Feldman S, Hughes W, Daniel C (1975) Varicella in children with cancer: 77 cases. Pediatrics 80:388–397Google Scholar
  15. Galea SA, Sweet A, Beninger P et al (2008). The safety profile of varicella vaccine: A 10-year review. J Infect Dis 197(Suppl 2):S165–S169CrossRefPubMedGoogle Scholar
  16. Gershon A, Steinberg S, Gelb L et al (1984) Live attenuated varicella vaccine: Efficacy for children with leukemia in remission. JAMA 252:355–362CrossRefPubMedGoogle Scholar
  17. Gershon A, LaRussa P, Steinberg S (1996a) Varicella vaccine: Use in immunocompromised patients. Infect Dis Clin North Am 10:583–594CrossRefPubMedGoogle Scholar
  18. Gershon A, LaRussa P, Steinberg S et al (1996b) The protective effect of immunologic boosting against zoster: An analysis in leukemic children who were vaccinated against chickenpox. J Infect Dis 173:450–453PubMedGoogle Scholar
  19. Gershon A, Takahashi M, Seward J (2008). Live attenuated varicella vaccine. In: Plotkin S, Orenstein W, Offit P (eds) Vaccines, 5th edn. WB Saunders, PhiladelphiaGoogle Scholar
  20. Hardy IB, Gershon A, Steinberg S et al (1991) The incidence of zoster after immunization with live attenuated varicella vaccine. A study in children with leukemia. N Engl J Med 325:1545–1550CrossRefPubMedGoogle Scholar
  21. Hattori A, Ihara T, Iwasa T et al (1976) Use of live varicella vaccine in children with acute leukemia or other malignancies (letter). Lancet 2:210CrossRefPubMedGoogle Scholar
  22. Hilleman MR, Buynak EB, Weibel RE et al (1968) Live, attenuated mumps-virus vaccine. N Engl J Med 278:227–232CrossRefPubMedGoogle Scholar
  23. Insinga RP, Itzler RF, Pellissier JM et al (2005) The incidence of herpes zoster in a United States administrative database. J Gen Intern Med 20:748–753CrossRefPubMedGoogle Scholar
  24. Izawa T, Ihara T, Hattori A et al (1977) Application of a live varicella vaccine in children with acute leukemia or other malignant diseases. Pediatrics 60:805–809PubMedGoogle Scholar
  25. Jumaan AO, Yu O, Jackson LA et al (2005) Incidence of herpes zoster, before and after varicella-vaccination-associated decreases in the incidence of varicella, 1992–2002. J Infect Dis 191:2002–2007CrossRefPubMedGoogle Scholar
  26. Kamiya H, Kato T, Isaji M et al (1984) Immunization of acute leukemic children with a live varicella vaccine (Oka strain). Biken J 27:99–102PubMedGoogle Scholar
  27. Katz SL, Medearis DN, Enders JF (1958) Experiences with live attenuated measles virus. Am J Dis Child 96:430Google Scholar
  28. Kempe CH, Gershon AA (1977) Varicella vaccine at the crossroads. Pediatrics 60:930–931PubMedGoogle Scholar
  29. Krugman S (1960) Varicella and herpes virus infections. Pediatr Clin North Am 7:881–902PubMedGoogle Scholar
  30. Krugman S, Goodrich CH, Ward R (1957) Primary varicella pneumonia. N Engl J Med 257:843–848CrossRefPubMedGoogle Scholar
  31. Kuter B, Matthews H, Shinefield H et al (2004) Ten year follow-up of healthy children who received one or two injections of varicella vaccine. Pediatr Infect Dis J 23:132–137CrossRefPubMedGoogle Scholar
  32. LaRussa P, Lungu O, Hardy I et al (1992) Restriction fragment length polymorphism of polymerase chain reaction products from vaccine and wild-type varicella-zoster virus isolates. J Virol 66:1016–1020PubMedGoogle Scholar
  33. Leung J, Molinari N, Harpaz R (2005) Trends in the incidence of herpes zoster using a national insurance database: United States 1993–2003. Presented at the 43rd Annual Infectious Disease Society of America Meeting, San Francisco, CA, 6–9 October 2005Google Scholar
  34. Levin MJ, Dahl KM, Weinberg A et al (2003) Development of resistance to acyclovir during chronic Oka strain varicella-zoster virus infection in an immunocompromised child. J Infect Dis 188:954–959CrossRefPubMedGoogle Scholar
  35. Levin MJ, Gershon AA, Weinberg A et al (2006) Administration of live varicella vaccine to HIV infected children with current or past significant depression of CD4(+) T cells. J Infect Dis 194:247–255CrossRefPubMedGoogle Scholar
  36. Loparev VN, Rubtcova E, Seward JF et al (2007) DNA sequence variability in isolates recovered from patients with post-vaccination rash or herpes zoster caused by Oka varicella vaccine. J Infect Dis 195:502–510CrossRefPubMedGoogle Scholar
  37. Lopez AS, Burnett-Hartman A, Nambiar R et al (2008). Transmission of a newly characterized strain of varicella-zoster virus from a patient with herpes zoster in a long term care facility, West Virginia, 2004. J Infect Dis 197:646–653CrossRefPubMedGoogle Scholar
  38. Michalik DE, Steinberg SP, LaRussa PS et al (2008) Primary vaccine failure after 1 dose of varicella vaccine in healthy children. J Infect Dis 197:944–949CrossRefPubMedGoogle Scholar
  39. Mullooly JP, Riedlinger K, Chun C et al (2005) Incidence of herpes zoster, 1997–2002. Epidemiol Infect 133:245–253CrossRefPubMedGoogle Scholar
  40. Neff BJ, Weibel RE, Villerajos VM et al (1981) Clinical and laboratory studies of KMcC strain of live attenuated varicella virus. Proc Soc Exp Biol Med 166:339–347PubMedGoogle Scholar
  41. Nguyen HQ, Jumaan AO, Seward JF (2005) Decline in mortality due to varicella after implementation of varicella vaccination in the United States. N Engl J Med 352:450–458CrossRefPubMedGoogle Scholar
  42. Oxman MN, Levin MJ, Johnson GR et al (2005) A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med 352:2271–2284CrossRefPubMedGoogle Scholar
  43. Plotkin SA, Farquhar JD, Katz M et al (1969) Attenuation of RA 27–3 rubella virus in WI-38 human diploid cells. Am J Dis Child 118:178–185PubMedGoogle Scholar
  44. Ragozzino ME, Melton LF, Kurland L et al (1982) Population-based study of herpes zoster and its sequelae. Medicine 61:310–316CrossRefPubMedGoogle Scholar
  45. Sabin AB, Hennessen WA, Winsser J (1954) Studies on variants of poliomyelitis virus. I. Experimental segregation and properties of avirulent variants of three immunologic types. J Exp Med 99:551–576CrossRefPubMedGoogle Scholar
  46. Sakurai N, Ihara T, Ito M et al (1982) Application of a live varicella vaccine in children with acute leukemia. Exerpta Medica, AmsterdamGoogle Scholar
  47. Seward JF, Orenstein WA (2006) Commentary: The case for universal varicella immunization. Pediatr Infect Dis J 25:45–46PubMedGoogle Scholar
  48. Seward JF, Watson BM, Peterson CL et al (2002) Varicella disease after introduction of varicella vaccine in the United States, 1995–2000. JAMA 287:606–611CrossRefPubMedGoogle Scholar
  49. Seward JF, Zhang JX, Maupin TJ et al (2004). Contagiousness of varicella in vaccinated cases: A household contact study. JAMA 292:704–708CrossRefPubMedGoogle Scholar
  50. Sharrar RG, LaRussa P, Galea S et al (2000) The postmarketing safety profile of varicella vaccine. Vaccine 19:916–923CrossRefPubMedGoogle Scholar
  51. Shinefield H, Black S, Digilio L et al (2005) Evaluation of a quadrivalent measles, mumps, rubella and varicella vaccine in healthy children. Pediatr Infect Dis J 24:665–669CrossRefPubMedGoogle Scholar
  52. Son M, Shapiro E, LaRussa P et al (2008). Vaccination of children with perinatal HIV infection protects against varicella and zoster. Paper presented at the Pediatric Academic Societies Annual Meeting, Honolulu, HI, 3–6 May 2008Google Scholar
  53. Takahashi M, Otsuka T, Okuno Y et al (1974) Live vaccine used to prevent the spread of varicella in children in hospital. Lancet 2:1288–1290CrossRefPubMedGoogle Scholar
  54. Takahashi M, Kamiya H, Baba K et al (1985) Clinical experience with Oka live varicella vaccine in Japan. Postgrad Med 61:61–67CrossRefGoogle Scholar
  55. Takahashi M, Baba K, Horiuchi K et al (1990) A live varicella vaccine. Advances in experimental medicine and biology, vol 278. Plenum, New YorkGoogle Scholar
  56. Theiler M, Smith HH (1937) The use of yellow fever virus modified by in vitro cultivation for human immunization. J Exp Med 65:787–800CrossRefPubMedGoogle Scholar
  57. Varis T, Vesikari T (1996) Efficacy of high titer live attenuated varicella vaccine in healthy young children. J Infect Dis 174:S330–S334PubMedGoogle Scholar
  58. Vazquez M, LaRussa P, Gershon A et al (2001) The effectiveness of the varicella vaccine in clinical practice. N Engl J Med 344:955–960CrossRefPubMedGoogle Scholar
  59. Vazquez M, LaRussa PS, Gershon AA et al (2004) Effectiveness over time of varicella vaccine. JAMA 291:851–855CrossRefPubMedGoogle Scholar
  60. Weibel R, Neff BJ, Kuter BJ et al (1984) Live attenuated varicella virus vaccine: Efficacy trial in healthy children. N Engl J Med 310:1409–1415CrossRefPubMedGoogle Scholar
  61. Weller TH (1992) Varicella and herpes zoster: A perspective and overview. J Infect Dis 166(Suppl 1):S1–S6PubMedGoogle Scholar
  62. Weller TH and Stoddard MB (1952) Intranuclear inclusion bodies in cultures of human tissue inoculated with varicella vesicle fluid. J Immunol 68:311–319PubMedGoogle Scholar
  63. White CJ (1996) Clinical trials of varicella vaccine in healthy children. Infect Dis Clin North Am 10:595–608CrossRefPubMedGoogle Scholar
  64. Williams V, Gershon A, Brunell P (1974) Serologic response to varicella-zoster membrane antigens measured by indirect immunofluorescence. J Infect Dis 130:669–672PubMedGoogle Scholar
  65. Wood MJ (2000) History of varicella zoster virus. Herpes 7(3):60–65PubMedGoogle Scholar
  66. Wood SM, Shah SS, Steenhoff AP et al (2008) Primary varicella and herpes zoster among HIV infected children from 1989 to 2006. Pediatrics 121:e150–e156CrossRefPubMedGoogle Scholar
  67. Yih WK, Brooks DR, Lett SM et al (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 5:68CrossRefPubMedGoogle Scholar
  68. Zhou F, Harpaz R, Jumaan AO et al (2005) Impact of varicella vaccination on health care utilization. JAMA 294:797–802CrossRefPubMedGoogle Scholar

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of PediatricsColumbia UniversityNew YorkUSA

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