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Vaccination for the prevention of shingles (herpes zoster)

Mary A Albrecht, MD
Section Editor
Martin S Hirsch, MD
Deputy Editor
Jennifer Mitty, MD, MPH


Varicella-zoster virus (VZV) infection causes two clinically distinct forms of disease. Primary infection with VZV results in varicella, known as chickenpox, characterized by vesicular lesions in different stages of development on the face, trunk, and extremities. Herpes zoster, also known as shingles, results from reactivation of endogenous latent VZV infection within the sensory ganglia. This clinical form of the disease is typically characterized by a painful, unilateral vesicular eruption that occurs in a restricted dermatomal distribution.

Vaccines are available for prevention of both infections. This topic will address the use of the inactivated recombinant and live attenuated zoster vaccine to prevent reactivation disease. A discussion of the vaccine used to prevent varicella (chickenpox) is found elsewhere. (See "Vaccination for the prevention of chickenpox (primary varicella infection)".)


Varicella-zoster virus (VZV)-specific cell-mediated immune responses plays a critical role in controlling VZV latency and limiting the potential for reactivation [1-4]. A decline in cell-mediated VZV-specific immunity has been documented in older individuals and in patients with lymphoproliferative malignancies who experience higher rates of herpes zoster [3-5]. In contrast, children with hypogammaglobulinemia do not experience severely protracted or fulminant primary varicella infection, or increased rates of zoster [6]. These combined observations suggest that a decline in cell-mediated, rather than humoral, immunity is linked directly to reactivated VZV syndromes. These epidemiologic observations are supported by in vitro data that demonstrate reduced VZV T cell responder cell frequency in aging patients who are more susceptible to virus activation [7].

Immunity and risk of reactivation — A decline in cell-mediated immunity to varicella-zoster is regarded as the major precipitant for inducing VZV reactivation [3-5]. Approximately 30 to 40 percent of persons over the age of 55 years do not have any detectable VZV-specific T cell responses [8].

Among those who develop herpes zoster, in vitro data suggest that robust VZV cell-mediated immunity, at the onset of rash, is correlated with reduced severity of disease and less risk of postherpetic neuralgia [9]. Immunocompromised patients who lack adequate VZV-specific cellular immune responses are at greater risk for prolonged episodes of reactivation and disseminated disease, which can be fatal [8]. (See "Clinical manifestations of varicella-zoster virus infection: Herpes zoster".)

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Literature review current through: Nov 2017. | This topic last updated: Nov 10, 2017.
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  1. Oxman MN. Immunization to reduce the frequency and severity of herpes zoster and its complications. Neurology 1995; 45:S41.
  2. Hardy I, Gershon AA, Steinberg SP, LaRussa P. The incidence of zoster after immunization with live attenuated varicella vaccine. A study in children with leukemia. Varicella Vaccine Collaborative Study Group. N Engl J Med 1991; 325:1545.
  3. Burke BL, Steele RW, Beard OW, et al. Immune responses to varicella-zoster in the aged. Arch Intern Med 1982; 142:291.
  4. Arvin AM. Aspects of the host response to varicella-zoster virus: a review of recent observations. Neurology 1995; 45:S36.
  5. Arvin AM, Pollard RB, Rasmussen LE, Merigan TC. Cellular and humoral immunity in the pathogenesis of recurrent herpes viral infections in patients with lymphoma. J Clin Invest 1980; 65:869.
  6. GOOD RA, ZAK SJ. Disturbances in gamma globulin synthesis as experiments of nature. Pediatrics 1956; 18:109.
  7. Hayward AR, Herberger M. Lymphocyte responses to varicella zoster virus in the elderly. J Clin Immunol 1987; 7:174.
  8. Weinberg A, Lazar AA, Zerbe GO, et al. Influence of age and nature of primary infection on varicella-zoster virus-specific cell-mediated immune responses. J Infect Dis 2010; 201:1024.
  9. Weinberg A, Zhang JH, Oxman MN, et al. Varicella-zoster virus-specific immune responses to herpes zoster in elderly participants in a trial of a clinically effective zoster vaccine. J Infect Dis 2009; 200:1068.
  10. Ljungman P, Lönnqvist B, Gahrton G, et al. Clinical and subclinical reactivations of varicella-zoster virus in immunocompromised patients. J Infect Dis 1986; 153:840.
  11. Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med 2005; 352:2271.
  12. Thomas SL, Wheeler JG, Hall AJ. Contacts with varicella or with children and protection against herpes zoster in adults: a case-control study. Lancet 2002; 360:678.
  13. Arvin AM, Koropchak CM, Wittek AE. Immunologic evidence of reinfection with varicella-zoster virus. J Infect Dis 1983; 148:200.
  14. Levin MJ, Oxman MN, Zhang JH, et al. Varicella-zoster virus-specific immune responses in elderly recipients of a herpes zoster vaccine. J Infect Dis 2008; 197:825.
  15. Leroux-Roels I, Leroux-Roels G, Clement F, et al. A phase 1/2 clinical trial evaluating safety and immunogenicity of a varicella zoster glycoprotein e subunit vaccine candidate in young and older adults. J Infect Dis 2012; 206:1280.
  16. Irwin MR, Levin MJ, Laudenslager ML, et al. Varicella zoster virus-specific immune responses to a herpes zoster vaccine in elderly recipients with major depression and the impact of antidepressant medications. Clin Infect Dis 2013; 56:1085.
  17. Morrison VA, Oxman MN, Levin MJ, et al. Safety of zoster vaccine in elderly adults following documented herpes zoster. J Infect Dis 2013; 208:559.
  18. Shingrix approved in the US for prevention of shingles in adults aged 50 and over. Press release available at https://www.gsk.com/en-gb/media/press-releases/shingrix-approved-in-the-us-for-prevention-of-shingles-in-adults-aged-50-and-over/ (Accessed on October 27, 2017).
  19. CDC Advisers Recommend New Herpes Zoster Vaccine over Zostavax. http://www.jwatch.org/fw113469/2017/10/26/cdc-advisers-recommend-new-herpes-zoster-vaccine-over (Accessed on October 27, 2017).
  20. Lal H, Cunningham AL, Godeaux O, et al. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. N Engl J Med 2015; 372:2087.
  21. Chlibek R, Smetana J, Pauksens K, et al. Safety and immunogenicity of three different formulations of an adjuvanted varicella-zoster virus subunit candidate vaccine in older adults: a phase II, randomized, controlled study. Vaccine 2014; 32:1745.
  22. Chlibek R, Bayas JM, Collins H, et al. Safety and immunogenicity of an AS01-adjuvanted varicella-zoster virus subunit candidate vaccine against herpes zoster in adults >=50 years of age. J Infect Dis 2013; 208:1953.
  23. Shingrix package insert. https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM581605.pdf (Accessed on October 27, 2017).
  24. Grupping K, Campora L, Douha M, et al. Immunogenicity and Safety of the HZ/su Adjuvanted Herpes Zoster Subunit Vaccine in Adults Previously Vaccinated with a Live-Attenuated Herpes Zoster Vaccine. J Infect Dis 2017.
  25. Cunningham AL, Lal H, Kovac M, et al. Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older. N Engl J Med 2016; 375:1019.
  26. Schwarz TF, Aggarwal N, Moeckesch B, et al. Immunogenicity and safety of an adjuvanted herpes zoster subunit vaccine co-administered with seasonal influenza vaccine in adults aged 50 years and older. J Infect Dis 2017.
  27. Harpaz R, Ortega-Sanchez IR, Seward JF, Advisory Committee on Immunization Practices (ACIP) Centers for Disease Control and Prevention (CDC). Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2008; 57:1.
  28. Hales CM, Harpaz R, Ortega-Sanchez I, et al. Update on recommendations for use of herpes zoster vaccine. MMWR Morb Mortal Wkly Rep 2014; 63:729.
  29. Kim DK, Riley LE, Harriman KH, et al. Recommended Immunization Schedule for Adults Aged 19 Years or Older, United States, 2017. Ann Intern Med 2017; 166:209.
  30. Gagliardi AM, Andriolo BN, Torloni MR, Soares BG. Vaccines for preventing herpes zoster in older adults. Cochrane Database Syst Rev 2016; 3:CD008858.
  31. Tseng HF, Smith N, Harpaz R, et al. Herpes zoster vaccine in older adults and the risk of subsequent herpes zoster disease. JAMA 2011; 305:160.
  32. Schmader KE, Levin MJ, Gnann JW Jr, et al. Efficacy, safety, and tolerability of herpes zoster vaccine in persons aged 50-59 years. Clin Infect Dis 2012; 54:922.
  33. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm248390.htm.
  34. Schmader KE, Oxman MN, Levin MJ, et al. Persistence of the efficacy of zoster vaccine in the shingles prevention study and the short-term persistence substudy. Clin Infect Dis 2012; 55:1320.
  35. Morrison VA, Johnson GR, Schmader KE, et al. Long-term persistence of zoster vaccine efficacy. Clin Infect Dis 2015; 60:900.
  36. Tseng HF, Harpaz R, Luo Y, et al. Declining Effectiveness of Herpes Zoster Vaccine in Adults Aged ≥60 Years. J Infect Dis 2016; 213:1872.
  37. Le P, Rothberg MB. Cost-Effectiveness of Herpes Zoster Vaccine for Persons Aged 50 Years. Ann Intern Med 2015; 163:489.
  38. Mills R, Tyring SK, Levin MJ, et al. Safety, tolerability, and immunogenicity of zoster vaccine in subjects with a history of herpes zoster. Vaccine 2010; 28:4204.
  39. Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014; 58:e44.
  40. Le DP, Vega J, Johnson LA. Notes from the Field: Hospital Contact Investigation for a Patient Who Developed a Zoster Vaccine-Related Rash - Maryland, February 2015. MMWR Morb Mortal Wkly Rep 2017; 66:763.
  41. Oxman MN. Zoster vaccine: current status and future prospects. Clin Infect Dis 2010; 51:197.
  42. Herpes zoster vaccine (Zostavax). Med Lett Drugs Ther 2006; 48:73.
  43. Kimberlin DW, Whitley RJ. Varicella-zoster vaccine for the prevention of herpes zoster. N Engl J Med 2007; 356:1338.
  44. Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol 2016; 68:1.
  45. Gilden DH. Varicella-zoster virus vaccine--grown-ups need it, too. N Engl J Med 2005; 352:2344.
  46. PNEUMOVAX 23 (pneumococcal vaccine polyvalent) sterile, liquid vaccine for intramuscular or subcutaneous injection - prescribing information. http://www.merck.com/product/usa/pi_circulars/p/pneumovax_23/pneumovax_pi.pdf (Accessed on October 24, 2013).
  47. MacIntyre CR, Egerton T, McCaughey M, et al. Concomitant administration of zoster and pneumococcal vaccines in adults ≥60 years old. Hum Vaccin 2010; 6:894.
  48. ZOSTAVAX (zoster vaccine live) - highlights of prescribing information. http://www.merck.com/product/usa/pi_circulars/z/zostavax/zostavax_pi2.pdf (Accessed on October 24, 2013).
  49. Wyman MJ, Stabi KL. Concomitant administration of pneumococcal-23 and zoster vaccines provides adequate herpes zoster coverage. Ann Pharmacother 2013; 47:1064.
  50. Centers for Disease Control and Prevention. Herpes zoster vaccination - information for health care professionals. http://www.cdc.gov/vaccines/vpd-vac/shingles/hcp-vaccination.htm (Accessed on October 24, 2013).
  51. Tseng HF, Smith N, Sy LS, Jacobsen SJ. Evaluation of the incidence of herpes zoster after concomitant administration of zoster vaccine and polysaccharide pneumococcal vaccine. Vaccine 2011; 29:3628.
  52. Simberkoff MS, Arbeit RD, Johnson GR, et al. Safety of herpes zoster vaccine in the shingles prevention study: a randomized trial. Ann Intern Med 2010; 152:545.
  53. Gagliardi AM, Gomes Silva BN, Torloni MR, Soares BG. Vaccines for preventing herpes zoster in older adults. Cochrane Database Syst Rev 2012; 10:CD008858.
  54. Charkoudian LD, Kaiser GM, Steinmetz RL, Srivastava SK. Acute retinal necrosis after herpes zoster vaccination. Arch Ophthalmol 2011; 129:1495.
  55. Gonzales JA, Levison AL, Stewart JM, et al. Retinal necrosis following varicella-zoster vaccination. Arch Ophthalmol 2012; 130:1355.
  56. Tseng HF, Schmid DS, Harpaz R, et al. Herpes zoster caused by vaccine-strain varicella zoster virus in an immunocompetent recipient of zoster vaccine. Clin Infect Dis 2014; 58:1125.
  57. Levin MJ, Schmader KE, Pang L, et al. Cellular and Humoral Responses to a Second Dose of Herpes Zoster Vaccine Administered 10 Years After the First Dose Among Older Adults. J Infect Dis 2016; 213:14.