Varicella‐Zoster Virus–Specific Immune Responses in Elderly Recipients of a Herpes Zoster Vaccine
1University of Colorado Health Sciences Center, Denver, Colorado; 2Department of Veterans Affairs San Diego Healthcare System and 3University of California, San Diego, 4Cousins Center for Psychoneuroimmunology, University of California, Los Angeles; 5Veterans Affairs Cooperative Studies Program Coordinating Center, West Haven, Connecticut; 6Merck Research Laboratories, Merck and Company, West Point, Pennsylvania; 7National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; 8Columbia University, New York, New York
Background.
A double‐blind, placebo‐controlled trial that involved 38,546 subjects 
60 years old demonstrated efficacy of a high‐potency live‐attenuated Oka/Merck varicella‐zoster virus (VZV) vaccine. The trial included an immunology substudy to determine the relationship of VZV‐specific immune responses to vaccination and clinical outcome.
Methods.The immunology substudy enrolled 1395 subjects at 2 sites where blood samples obtained prior to vaccination, at 6 weeks after vaccination, and at 1, 2, and 3 years thereafter were tested for VZV‐specific cell‐mediated immunity (VZV‐CMI) by γ‐interferon ELISPOT and responder cell frequency assays and for VZV antibody by glycoprotein ELISA.
Results.VZV‐CMI and VZV antibodies were significantly increased in vaccine recipients at 6 weeks after vaccination. The vaccine‐induced increases in VZV‐CMI persisted during the 3 years of follow‐up, although their magnitude decreased over time. The magnitude of these VZV‐specific immune responses was greater in subjects 60–69 years old than in subjects 70 years old.
Conclusions.The zoster vaccine induced a significant increase in VZV‐CMI and VZV antibody. The magnitude and duration of the boost in VZV‐CMI in vaccine recipients and the relationship of this boost to age paralleled the clinical effects of the vaccine observed during the efficacy trial. These findings support the hypothesis that boosting VZV‐CMI protects older adults against herpes zoster and postherpetic neuralgia.
Received 18 July 2007; accepted 10 October 2007; electronically published 21 February 2008.
Cited by
Online publication date: 1-Aug-2009.
CrossRef
Online publication date: 1-Aug-2008.
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Presented in part: 44th annual meeting of the Infectious Diseases Society of America, Toronto, 2006 (abstract 858), and the 4th Congress of the European Union Geriatric Medicine Society, Geneva, Switzerland, 2006 (abstract PP192).
Potential conflicts of interest: M.J.L. claims intellectual property in a Merck & Co. patent on the use of VZV vaccine to prevent herpes zoster. M.J.L., A.W., and A.G. receive research funds and/or consultation fees from Merck & Co., or are on their Speakers Bureau. I.S.F.C., M.C., J.S., J.C., and R.M. are employees of Merck & Co., Inc. Merck stock or stock options are held by I.S.F.C., R.H., and H.W. (less than $10,000).
Financial support: National Institute of Child Health and Human Development (grant contract N01‐HD‐3–3345 to M.J.L.); Health Resources and Services Administration (H12HA00070 and NIAID U01 AI068632 to M.J.L.); Cousins Center for Psychoneuroimmunology (grant to M.R.I.); NHLBI (grant R01 HL079955 to M.R.I.); NIA (grants R01 AG026364 and R01 AG026006–01 to M.R.I.); NCF (grant R01 CA 10014152 to M.R.I.); NIMH (grant T32MH19925 to M.R.I.); NIPS (grant P60 AG 10415 to M.R.I.); NCRR (grant M01‐RR00865 to M.R.I.); and NIAMS (grants R01 NR009228 and R01 AR049840 to M.R.I.). Additional support was provided by the National Institute of Allergy and Infectious Diseases, Merck & Co., the National Institutes of Health (grant NIMH R01 MH 55253 to M.J.I.), and by the James R. and Jesse V. Scott Fund for Shingles Research (to M.N.O.).
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Deceased.
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Veterans Affairs Cooperative Studies Program Shingles Prevention Study Investigators are listed after the text.