Safety, tolerability, and immunogenicity after 1 and 2 doses of zoster vaccine in healthy adults ≥60 years of age

Joost N. Vermeulen; Joep M.A. Lange; Stephen K. Tyring; Patrick H. Peters; Margaret Nunez; Gregory Poland; Myron J. Levin; Carrie Freeman; Ira Chalikonda; Jianjun Li; Jeffrey G. Smith; Michael J. Caulfield; Jon E. Stek; Ivan S.F. Chan; Rupert Vessey; Florian P. Schödel; Paula W. Annunziato; Katia Schlienger; Jeffrey L. Silber

doi:10.1016/j.vaccine.2011.11.096

Safety, tolerability, and immunogenicity after 1 and 2 doses of zoster vaccine in healthy adults ≥60 years of age

Joost N. Vermeulen, Joep M.A. Lange, Stephen K. Tyring, Patrick H. Peters, Margaret Nunez, Gregory Poland, Myron J. Levin, Carrie Freeman, Ira Chalikonda, Jianjun Li, Jeffrey G. Smith, Michael J. Caulfield, Jon E. Stek, Ivan S.F. Chan, Rupert Vessey, Florian P. Schödel, Paula W. Annunziato, Katia Schlienger, Jeffrey L. Silber

General Internal Medicine

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

41 Scopus citations

Abstract

Background: Incidence and severity of herpes zoster (HZ) and postherpetic neuralgia increase with age, associated with age-related decrease in immunity to varicella-zoster virus (VZV). One dose of zoster vaccine (ZV) has demonstrated substantial protection against HZ; this study examined impact of a second dose of ZV. Methods: Randomized, double-blind, multicenter study with 210 subjects ≥60 years old compared immunity and safety profiles after one and two doses of ZV, separated by 6 weeks, vs. placebo. Immunogenicity was evaluated using VZV interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assay and VZV glycoprotein enzyme-linked immunosorbent antibody (gpELISA) assay. Adverse experiences (AEs) were recorded on a standardized Vaccination Report Card. Results: No serious vaccine-related AEs occurred. VZV IFN-γ ELISPOT geometric mean count (GMC) of spot-forming cells per 10 ⁶ peripheral blood mononuclear cells increased in the ZV group from 16.9 prevaccination to 49.5 and 32.8 at 2 and 6 weeks postdose 1, respectively. Two weeks, 6 weeks and 6 months postdose 2, GMC was 44.3, 42.9, and 36.5, respectively. GMC in the placebo group did not change during the study. The peak ELISPOT response occurred ∼2 weeks after each ZV dose. The gpELISA geometric mean titers (GMTs) in the ZV group were higher than in the placebo group at 6 weeks after each dose. Correlation between the IFN-γ ELISPOT and gpELISA assays was poor. Conclusions: ZV was generally well-tolerated and immunogenic in adults ≥60 years old. A second dose of ZV was generally safe, but did not boost VZV-specific immunity beyond levels achieved postdose 1.

Original language	English (US)
Pages (from-to)	904-910
Number of pages	7
Journal	Vaccine
Volume	30
Issue number	5
DOIs	https://doi.org/10.1016/j.vaccine.2011.11.096
State	Published - Jan 20 2012

Keywords

Herpes zoster
Immunogenicity
Safety
Vaccine

ASJC Scopus subject areas

Molecular Medicine
Immunology and Microbiology(all)
veterinary(all)
Public Health, Environmental and Occupational Health
Infectious Diseases

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10.1016/j.vaccine.2011.11.096

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Vermeulen, J. N., Lange, J. M. A., Tyring, S. K., Peters, P. H., Nunez, M., Poland, G., Levin, M. J., Freeman, C., Chalikonda, I., Li, J., Smith, J. G., Caulfield, M. J., Stek, J. E., Chan, I. S. F., Vessey, R., Schödel, F. P., Annunziato, P. W., Schlienger, K., & Silber, J. L. (2012). Safety, tolerability, and immunogenicity after 1 and 2 doses of zoster vaccine in healthy adults ≥60 years of age. Vaccine, 30(5), 904-910. https://doi.org/10.1016/j.vaccine.2011.11.096

Vermeulen, JN, Lange, JMA, Tyring, SK, Peters, PH, Nunez, M, Poland, G, Levin, MJ, Freeman, C, Chalikonda, I, Li, J, Smith, JG, Caulfield, MJ, Stek, JE, Chan, ISF, Vessey, R, Schödel, FP, Annunziato, PW, Schlienger, K & Silber, JL 2012, 'Safety, tolerability, and immunogenicity after 1 and 2 doses of zoster vaccine in healthy adults ≥60 years of age', Vaccine, vol. 30, no. 5, pp. 904-910. https://doi.org/10.1016/j.vaccine.2011.11.096

@article{ae0d33b30d80402eac4dd6dfdd829efc,

title = "Safety, tolerability, and immunogenicity after 1 and 2 doses of zoster vaccine in healthy adults ≥60 years of age",

abstract = "Background: Incidence and severity of herpes zoster (HZ) and postherpetic neuralgia increase with age, associated with age-related decrease in immunity to varicella-zoster virus (VZV). One dose of zoster vaccine (ZV) has demonstrated substantial protection against HZ; this study examined impact of a second dose of ZV. Methods: Randomized, double-blind, multicenter study with 210 subjects ≥60 years old compared immunity and safety profiles after one and two doses of ZV, separated by 6 weeks, vs. placebo. Immunogenicity was evaluated using VZV interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assay and VZV glycoprotein enzyme-linked immunosorbent antibody (gpELISA) assay. Adverse experiences (AEs) were recorded on a standardized Vaccination Report Card. Results: No serious vaccine-related AEs occurred. VZV IFN-γ ELISPOT geometric mean count (GMC) of spot-forming cells per 10 6 peripheral blood mononuclear cells increased in the ZV group from 16.9 prevaccination to 49.5 and 32.8 at 2 and 6 weeks postdose 1, respectively. Two weeks, 6 weeks and 6 months postdose 2, GMC was 44.3, 42.9, and 36.5, respectively. GMC in the placebo group did not change during the study. The peak ELISPOT response occurred ∼2 weeks after each ZV dose. The gpELISA geometric mean titers (GMTs) in the ZV group were higher than in the placebo group at 6 weeks after each dose. Correlation between the IFN-γ ELISPOT and gpELISA assays was poor. Conclusions: ZV was generally well-tolerated and immunogenic in adults ≥60 years old. A second dose of ZV was generally safe, but did not boost VZV-specific immunity beyond levels achieved postdose 1.",

keywords = "Herpes zoster, Immunogenicity, Safety, Vaccine",

author = "Vermeulen, {Joost N.} and Lange, {Joep M.A.} and Tyring, {Stephen K.} and Peters, {Patrick H.} and Margaret Nunez and Gregory Poland and Levin, {Myron J.} and Carrie Freeman and Ira Chalikonda and Jianjun Li and Smith, {Jeffrey G.} and Caulfield, {Michael J.} and Stek, {Jon E.} and Chan, {Ivan S.F.} and Rupert Vessey and Sch{\"o}del, {Florian P.} and Annunziato, {Paula W.} and Katia Schlienger and Silber, {Jeffrey L.}",

note = "Funding Information: Financial disclosure: Other than employees of Merck Sharp & Dohme Corp. (as indicated on the title page), all authors have been investigators for the sponsor. Dr. Levin is a consultant for Merck and shares intellectual property in the zoster vaccine. Employees may hold stock and/or stock options in the company. Contributors: Vermeulen, Lange, Tyring, Peters, Nunez, Poland, Levin – subject enrollment, data collection, data interpretation, and manuscript preparation; Chalikonda, Li, Chan, Vessey, Sch{\"o}del, Schlienger, Silber – study concept/design, data analysis/interpretation, and manuscript preparation; Smith, Caulfield – data collection, data analysis/interpretation, and manuscript preparation; and Freeman, Stek, Annunziato – data analysis/interpretation, and manuscript preparation. Sponsor's role: This study was funded by Merck Sharp & Dohme Corp. (sponsor). In conjunction with the external investigators, this study was designed, executed, and analyzed by the sponsor. Although the sponsor formally reviewed a penultimate draft, the opinions expressed are those of the authorship and may not necessarily reflect those of the sponsor. All co-authors approved the final version of the manuscript.",

year = "2012",

month = jan,

day = "20",

doi = "10.1016/j.vaccine.2011.11.096",

language = "English (US)",

volume = "30",

pages = "904--910",

journal = "Vaccine",

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number = "5",

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TY - JOUR

T1 - Safety, tolerability, and immunogenicity after 1 and 2 doses of zoster vaccine in healthy adults ≥60 years of age

AU - Vermeulen, Joost N.

AU - Lange, Joep M.A.

AU - Tyring, Stephen K.

AU - Peters, Patrick H.

AU - Nunez, Margaret

AU - Poland, Gregory

AU - Levin, Myron J.

AU - Freeman, Carrie

AU - Chalikonda, Ira

AU - Li, Jianjun

AU - Smith, Jeffrey G.

AU - Caulfield, Michael J.

AU - Stek, Jon E.

AU - Chan, Ivan S.F.

AU - Vessey, Rupert

AU - Schödel, Florian P.

AU - Annunziato, Paula W.

AU - Schlienger, Katia

AU - Silber, Jeffrey L.

N1 - Funding Information: Financial disclosure: Other than employees of Merck Sharp & Dohme Corp. (as indicated on the title page), all authors have been investigators for the sponsor. Dr. Levin is a consultant for Merck and shares intellectual property in the zoster vaccine. Employees may hold stock and/or stock options in the company. Contributors: Vermeulen, Lange, Tyring, Peters, Nunez, Poland, Levin – subject enrollment, data collection, data interpretation, and manuscript preparation; Chalikonda, Li, Chan, Vessey, Schödel, Schlienger, Silber – study concept/design, data analysis/interpretation, and manuscript preparation; Smith, Caulfield – data collection, data analysis/interpretation, and manuscript preparation; and Freeman, Stek, Annunziato – data analysis/interpretation, and manuscript preparation. Sponsor's role: This study was funded by Merck Sharp & Dohme Corp. (sponsor). In conjunction with the external investigators, this study was designed, executed, and analyzed by the sponsor. Although the sponsor formally reviewed a penultimate draft, the opinions expressed are those of the authorship and may not necessarily reflect those of the sponsor. All co-authors approved the final version of the manuscript.

PY - 2012/1/20

Y1 - 2012/1/20

N2 - Background: Incidence and severity of herpes zoster (HZ) and postherpetic neuralgia increase with age, associated with age-related decrease in immunity to varicella-zoster virus (VZV). One dose of zoster vaccine (ZV) has demonstrated substantial protection against HZ; this study examined impact of a second dose of ZV. Methods: Randomized, double-blind, multicenter study with 210 subjects ≥60 years old compared immunity and safety profiles after one and two doses of ZV, separated by 6 weeks, vs. placebo. Immunogenicity was evaluated using VZV interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assay and VZV glycoprotein enzyme-linked immunosorbent antibody (gpELISA) assay. Adverse experiences (AEs) were recorded on a standardized Vaccination Report Card. Results: No serious vaccine-related AEs occurred. VZV IFN-γ ELISPOT geometric mean count (GMC) of spot-forming cells per 10 6 peripheral blood mononuclear cells increased in the ZV group from 16.9 prevaccination to 49.5 and 32.8 at 2 and 6 weeks postdose 1, respectively. Two weeks, 6 weeks and 6 months postdose 2, GMC was 44.3, 42.9, and 36.5, respectively. GMC in the placebo group did not change during the study. The peak ELISPOT response occurred ∼2 weeks after each ZV dose. The gpELISA geometric mean titers (GMTs) in the ZV group were higher than in the placebo group at 6 weeks after each dose. Correlation between the IFN-γ ELISPOT and gpELISA assays was poor. Conclusions: ZV was generally well-tolerated and immunogenic in adults ≥60 years old. A second dose of ZV was generally safe, but did not boost VZV-specific immunity beyond levels achieved postdose 1.

AB - Background: Incidence and severity of herpes zoster (HZ) and postherpetic neuralgia increase with age, associated with age-related decrease in immunity to varicella-zoster virus (VZV). One dose of zoster vaccine (ZV) has demonstrated substantial protection against HZ; this study examined impact of a second dose of ZV. Methods: Randomized, double-blind, multicenter study with 210 subjects ≥60 years old compared immunity and safety profiles after one and two doses of ZV, separated by 6 weeks, vs. placebo. Immunogenicity was evaluated using VZV interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assay and VZV glycoprotein enzyme-linked immunosorbent antibody (gpELISA) assay. Adverse experiences (AEs) were recorded on a standardized Vaccination Report Card. Results: No serious vaccine-related AEs occurred. VZV IFN-γ ELISPOT geometric mean count (GMC) of spot-forming cells per 10 6 peripheral blood mononuclear cells increased in the ZV group from 16.9 prevaccination to 49.5 and 32.8 at 2 and 6 weeks postdose 1, respectively. Two weeks, 6 weeks and 6 months postdose 2, GMC was 44.3, 42.9, and 36.5, respectively. GMC in the placebo group did not change during the study. The peak ELISPOT response occurred ∼2 weeks after each ZV dose. The gpELISA geometric mean titers (GMTs) in the ZV group were higher than in the placebo group at 6 weeks after each dose. Correlation between the IFN-γ ELISPOT and gpELISA assays was poor. Conclusions: ZV was generally well-tolerated and immunogenic in adults ≥60 years old. A second dose of ZV was generally safe, but did not boost VZV-specific immunity beyond levels achieved postdose 1.

KW - Herpes zoster

KW - Immunogenicity

KW - Safety

KW - Vaccine

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ER -

Safety, tolerability, and immunogenicity after 1 and 2 doses of zoster vaccine in healthy adults ≥60 years of age

Abstract

Keywords

ASJC Scopus subject areas

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