Varicella-zoster virus-specific immune responses in elderly recipients of a herpes zoster vaccine

Myron J. Levin; M. N. Oxman; J. H. Zhang; G. R. Johnson; H. Stanley; A. R. Hayward; M. J. Caulfield; M. R. Irwin; J. G. Smith; J. Clair; I. S F Chan; H. Williams; R. Harbecke; R. Marchese; S. E. Straus; A. Gershon; A. Weinberg; Michael N. Oxman; Robert Arbeit; Patricia Barry; Chris Beisel; Kathy D. Boardman; Cindy L. Colling; Larry Davis; Lawrence Gelb; Anne A. Gershon; Anthony R. Hayward; Michael R. Irwin; Gary R. Johnson; Peter N. Peduzzi; Kenneth Schmader; Michael S. Simberkoff; Stephen E. Straus; Adriana Weinberg; Heather M. Williams; Jeffrey L. Silber; Paula Annunziato; Christina Y. Chan; Ivan S F Chan; L. E. Davis; C. A. Kauffman; S. K. Keay; A. R. Marques; N. E. Soto; P. Brunell; J. W. Gnann; R. Serrao; D. J. Cotton; R. P. Goodman; R. D. Arbeit; C. T. Pachucki; M. J. Levin; K. E. Schmader; W. A. Keitel; R. N. Greenberg; V. A. Morrison; P. F. Wright; M. R. Griffin; M. S. Simberkoff; S. S. Yeh; Z. Lobo; M. Holodniy; J. Loutit; R. F. Betts; L. D. Gelb; G. E. Crawford; J. Guatelli; P. A. Brooks; K. M. Neuzil; J. F. Toney

doi:10.1086/528696

Varicella-zoster virus-specific immune responses in elderly recipients of a herpes zoster vaccine

Myron J. Levin, M. N. Oxman, J. H. Zhang, G. R. Johnson, H. Stanley, A. R. Hayward, M. J. Caulfield, M. R. Irwin, J. G. Smith, J. Clair, I. S F Chan, H. Williams, R. Harbecke, R. Marchese, S. E. Straus, A. Gershon, A. Weinberg, Michael N. Oxman, Robert Arbeit, Patricia BarryChris Beisel, Kathy D. Boardman, Cindy L. Colling, Larry Davis, Lawrence Gelb, Anne A. Gershon, Anthony R. Hayward, Michael R. Irwin, Gary R. Johnson, Peter N. Peduzzi, Kenneth Schmader, Michael S. Simberkoff, Stephen E. Straus, Adriana Weinberg, Heather M. Williams, Jeffrey L. Silber, Paula Annunziato, Christina Y. Chan, Ivan S F Chan, L. E. Davis, C. A. Kauffman, S. K. Keay, A. R. Marques, N. E. Soto, P. Brunell, J. W. Gnann, R. Serrao, D. J. Cotton, R. P. Goodman, R. D. Arbeit, C. T. Pachucki, M. J. Levin, K. E. Schmader, W. A. Keitel, R. N. Greenberg, V. A. Morrison, P. F. Wright, M. R. Griffin, M. S. Simberkoff, S. S. Yeh, Z. Lobo, M. Holodniy, J. Loutit, R. F. Betts, L. D. Gelb, G. E. Crawford, J. Guatelli, P. A. Brooks, K. M. Neuzil, J. F. Toney

Medicine - Veteran's Administration Medical Center

Research output: Contribution to journal › Article › peer-review

308 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	825-835
Number of pages	11
Journal	Journal of Infectious Diseases
Volume	197
Issue number	6
DOIs	https://doi.org/10.1086/528696
State	Published - Mar 15 2008

Bibliographical note

Funding Information:
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.). a Deceased.

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Levin, M. J., Oxman, M. N., Zhang, J. H., Johnson, G. R., Stanley, H., Hayward, A. R., Caulfield, M. J., Irwin, M. R., Smith, J. G., Clair, J., Chan, I. S. F., Williams, H., Harbecke, R., Marchese, R., Straus, S. E., Gershon, A., Weinberg, A., Oxman, M. N., Arbeit, R., ... Toney, J. F. (2008). Varicella-zoster virus-specific immune responses in elderly recipients of a herpes zoster vaccine. Journal of Infectious Diseases, 197(6), 825-835. https://doi.org/10.1086/528696

Levin, MJ, Oxman, MN, Zhang, JH, Johnson, GR, Stanley, H, Hayward, AR, Caulfield, MJ, Irwin, MR, Smith, JG, Clair, J, Chan, ISF, Williams, H, Harbecke, R, Marchese, R, Straus, SE, Gershon, A, Weinberg, A, Oxman, MN, Arbeit, R, Barry, P, Beisel, C, Boardman, KD, Colling, CL, Davis, L, Gelb, L, Gershon, AA, Hayward, AR, Irwin, MR, Johnson, GR, Peduzzi, PN, Schmader, K, Simberkoff, MS, Straus, SE, Weinberg, A, Williams, HM, Silber, JL, Annunziato, P, Chan, CY, Chan, ISF, Davis, LE, Kauffman, CA, Keay, SK, Marques, AR, Soto, NE, Brunell, P, Gnann, JW, Serrao, R, Cotton, DJ, Goodman, RP, Arbeit, RD, Pachucki, CT, Levin, MJ, Schmader, KE, Keitel, WA, Greenberg, RN, Morrison, VA, Wright, PF, Griffin, MR, Simberkoff, MS, Yeh, SS, Lobo, Z, Holodniy, M, Loutit, J, Betts, RF, Gelb, LD, Crawford, GE, Guatelli, J, Brooks, PA, Neuzil, KM & Toney, JF 2008, 'Varicella-zoster virus-specific immune responses in elderly recipients of a herpes zoster vaccine', Journal of Infectious Diseases, vol. 197, no. 6, pp. 825-835. https://doi.org/10.1086/528696

@article{d2ba6e2cc91749ca952962848f0a7a9e,

title = "Varicella-zoster virus-specific immune responses in elderly recipients of a herpes zoster vaccine",

abstract = "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.",

author = "Levin, {Myron J.} and Oxman, {M. N.} and Zhang, {J. H.} and Johnson, {G. R.} and H. Stanley and Hayward, {A. R.} and Caulfield, {M. J.} and Irwin, {M. R.} and Smith, {J. G.} and J. Clair and Chan, {I. S F} and H. Williams and R. Harbecke and R. Marchese and Straus, {S. E.} and A. Gershon and A. Weinberg and Oxman, {Michael N.} and Robert Arbeit and Patricia Barry and Chris Beisel and Boardman, {Kathy D.} and Colling, {Cindy L.} and Larry Davis and Lawrence Gelb and Gershon, {Anne A.} and Hayward, {Anthony R.} and Irwin, {Michael R.} and Johnson, {Gary R.} and Peduzzi, {Peter N.} and Kenneth Schmader and Simberkoff, {Michael S.} and Straus, {Stephen E.} and Adriana Weinberg and Williams, {Heather M.} and Silber, {Jeffrey L.} and Paula Annunziato and Chan, {Christina Y.} and Chan, {Ivan S F} and Davis, {L. E.} and Kauffman, {C. A.} and Keay, {S. K.} and Marques, {A. R.} and Soto, {N. E.} and P. Brunell and Gnann, {J. W.} and R. Serrao and Cotton, {D. J.} and Goodman, {R. P.} and Arbeit, {R. D.} and Pachucki, {C. T.} and Levin, {M. J.} and Schmader, {K. E.} and Keitel, {W. A.} and Greenberg, {R. N.} and Morrison, {V. A.} and Wright, {P. F.} and Griffin, {M. R.} and Simberkoff, {M. S.} and Yeh, {S. S.} and Z. Lobo and M. Holodniy and J. Loutit and Betts, {R. F.} and Gelb, {L. D.} and Crawford, {G. E.} and J. Guatelli and Brooks, {P. A.} and Neuzil, {K. M.} and Toney, {J. F.}",

note = "Funding Information: 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.). a Deceased.",

year = "2008",

month = mar,

day = "15",

doi = "10.1086/528696",

language = "English (US)",

volume = "197",

pages = "825--835",

journal = "Journal of Infectious Diseases",

issn = "0022-1899",

publisher = "Oxford University Press",

number = "6",

}

TY - JOUR

T1 - Varicella-zoster virus-specific immune responses in elderly recipients of a herpes zoster vaccine

AU - Levin, Myron J.

AU - Oxman, M. N.

AU - Zhang, J. H.

AU - Johnson, G. R.

AU - Stanley, H.

AU - Hayward, A. R.

AU - Caulfield, M. J.

AU - Irwin, M. R.

AU - Smith, J. G.

AU - Clair, J.

AU - Chan, I. S F

AU - Williams, H.

AU - Harbecke, R.

AU - Marchese, R.

AU - Straus, S. E.

AU - Gershon, A.

AU - Weinberg, A.

AU - Oxman, Michael N.

AU - Arbeit, Robert

AU - Barry, Patricia

AU - Beisel, Chris

AU - Boardman, Kathy D.

AU - Colling, Cindy L.

AU - Davis, Larry

AU - Gelb, Lawrence

AU - Gershon, Anne A.

AU - Hayward, Anthony R.

AU - Irwin, Michael R.

AU - Johnson, Gary R.

AU - Peduzzi, Peter N.

AU - Schmader, Kenneth

AU - Simberkoff, Michael S.

AU - Straus, Stephen E.

AU - Weinberg, Adriana

AU - Williams, Heather M.

AU - Silber, Jeffrey L.

AU - Annunziato, Paula

AU - Chan, Christina Y.

AU - Chan, Ivan S F

AU - Davis, L. E.

AU - Kauffman, C. A.

AU - Keay, S. K.

AU - Marques, A. R.

AU - Soto, N. E.

AU - Brunell, P.

AU - Gnann, J. W.

AU - Serrao, R.

AU - Cotton, D. J.

AU - Goodman, R. P.

AU - Arbeit, R. D.

AU - Pachucki, C. T.

AU - Levin, M. J.

AU - Schmader, K. E.

AU - Keitel, W. A.

AU - Greenberg, R. N.

AU - Morrison, V. A.

AU - Wright, P. F.

AU - Griffin, M. R.

AU - Simberkoff, M. S.

AU - Yeh, S. S.

AU - Lobo, Z.

AU - Holodniy, M.

AU - Loutit, J.

AU - Betts, R. F.

AU - Gelb, L. D.

AU - Crawford, G. E.

AU - Guatelli, J.

AU - Brooks, P. A.

AU - Neuzil, K. M.

AU - Toney, J. F.

N1 - Funding Information: 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.). a Deceased.

PY - 2008/3/15

Y1 - 2008/3/15

N2 - 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.

AB - 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.

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UR - http://www.scopus.com/inward/citedby.url?scp=40949123970&partnerID=8YFLogxK

U2 - 10.1086/528696

DO - 10.1086/528696

M3 - Article

C2 - 18419349

AN - SCOPUS:40949123970

SN - 0022-1899

VL - 197

SP - 825

EP - 835

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 6

ER -

Varicella-zoster virus-specific immune responses in elderly recipients of a herpes zoster vaccine

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