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J Infect Dis. 2014 Nov 15;210(10):1573-81. doi: 10.1093/infdis/jiu279. Epub 2014 May 13.

Fold rise in antibody titers by measured by glycoprotein-based enzyme-linked immunosorbent assay is an excellent correlate of protection for a herpes zoster vaccine, demonstrated via the vaccine efficacy curve.

Author information

  • 1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center and Department of Biostatistics, University of Washington.
  • 2National Institute of Allergy and Infectious Diseases, Biostatistics Research Branch, Bethesda, Maryland.
  • 3Department of Biometrics, Biogen Idec, Cambridge, Massachusetts.
  • 4Biostatistics, Gilead Sciences, Seattle, Washington.
  • 5Merck, Whitehouse Station, New Jersey.

Abstract

BACKGROUND:

The phase III Zostavax Efficacy and Safety Trial of 1 dose of licensed zoster vaccine (ZV; Zostavax; Merck) in 50-59-year-olds showed approximately 70% vaccine efficacy (VE) to reduce the incidence of herpes zoster (HZ). An objective of the trial was to assess immune response biomarkers measuring antibodies to varicella zoster virus (VZV) by glycoprotein-based enzyme-linked immunosorbent assay as correlates of protection (CoPs) against HZ.

METHODS:

The principal stratification vaccine efficacy curve framework for statistically evaluating immune response biomarkers as CoPs was applied. The VE curve describes how VE against the clinical end point (HZ) varies across participant subgroups defined by biomarker readout measuring vaccine-induced immune response. The VE curve was estimated using several subgroup definitions.

RESULTS:

The fold rise in VZV antibody titers from the time before immunization to 6 weeks after immunization was an excellent CoP, with VE increasing sharply with fold rise: VE was estimated at 0% for the subgroup with no rise and at 90% for the subgroup with 5.26-fold rise. In contrast, VZV antibody titers measured 6 weeks after immunization did not predict VE, with similar estimated VEs across titer subgroups.

CONCLUSIONS:

The analysis illustrates the value of the VE curve framework for assessing immune response biomarkers as CoPs in vaccine efficacy trials.

CLINICAL TRIALS REGISTRATION:

NCT00534248.

© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

KEYWORDS:

causal inference; correlate of immunity; immune correlate of protection; principal stratification; signature of protection; statistical analysis; surrogate endpoint; vaccine efficacy trial

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