Safety of herpes zoster vaccine in the shingles prevention study: a randomized trial

Ann Intern Med. 2010 May 4;152(9):545-54. doi: 10.7326/0003-4819-152-9-201005040-00004.


Background: The herpes zoster vaccine is effective in preventing herpes zoster and postherpetic neuralgia in immunocompetent older adults. However, its safety has not been described in depth.

Objective: To describe local adverse effects and short- and long-term safety profiles of herpes zoster vaccine in immunocompetent older adults.

Design: Randomized, placebo-controlled trial with enrollment from November 1998 to September 2001 and follow-up through April 2004 (mean, 3.4 years). A Veterans Affairs Coordinating Center generated the permutated block randomization scheme, which was stratified by site and age. Participants and follow-up study personnel were blinded to treatment assignments. ( registration number: NCT00007501)

Setting: 22 U.S. academic centers.

Participants: 38 546 immunocompetent adults 60 years or older, including 6616 who participated in an adverse events substudy.

Intervention: Single dose of herpes zoster vaccine or placebo.

Measurements: Serious adverse events and rashes in all participants and inoculation-site events in substudy participants during the first 42 days after inoculation. Thereafter, vaccination-related serious adverse events and deaths were monitored in all participants, and hospitalizations were monitored in substudy participants.

Results: After inoculation, 255 (1.4%) vaccine recipients and 254 (1.4%) placebo recipients reported serious adverse events. Local inoculation-site side effects were reported by 1604 (48%) vaccine recipients and 539 (16%) placebo recipients in the substudy. A total of 977 (56.6%) of the vaccine recipients reporting local side effects were aged 60 to 69 years, and 627 (39.2%) were older than 70 years. After inoculation, herpes zoster occurred in 7 vaccine recipients versus 24 placebo recipients. Long-term follow-up (mean, 3.39 years) showed that rates of hospitalization or death did not differ between vaccine and placebo recipients.

Limitations: Participants in the substudy were not randomly selected. Confirmation of reported serious adverse events with medical record data was not always obtained.

Conclusion: Herpes zoster vaccine is well tolerated in older, immunocompetent adults.

Primary funding source: Cooperative Studies Program, Department of Veterans Affairs, Office of Research and Development; grants from Merck to the Veterans Affairs Cooperative Studies Program; and the James R. and Jesse V. Scott Fund for Shingles Research.

Publication types

  • Comment
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Double-Blind Method
  • Herpes Zoster / prevention & control*
  • Herpes Zoster Vaccine / adverse effects*
  • Humans
  • Immunocompetence
  • Middle Aged
  • Neuralgia, Postherpetic / prevention & control*
  • Risk Factors


  • Herpes Zoster Vaccine

Associated data