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.
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.


BACKGROUND
NCT00534248.
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center and Department of Biostatistics, University of Washington.
Peter B
PB
Gilbert
National Institute of Allergy and Infectious Diseases, Biostatistics Research Branch, Bethesda, Maryland.
Erin E
EE
Gabriel
Department of Biometrics, Biogen Idec, Cambridge, Massachusetts.
Xiaopeng
X
Miao
Biostatistics, Gilead Sciences, Seattle, Washington.
Xiaoming
X
Li
Merck, Whitehouse Station, New Jersey.
Shu-Chih
SC
Su
Merck, Whitehouse Station, New Jersey.
Janie
J
Parrino
Merck, Whitehouse Station, New Jersey.
Ivan S F
IS
Chan
D000914:Antibodies, Viral / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006562:Herpes Zoster / Q000276:immunology / Q000517:prevention & control*; D053061:Herpes Zoster Vaccine / Q000008:administration & dosage / Q000276:immunology*; D014645:Herpesvirus 3, Human / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged
D000914:Antibodies, Viral; D015415:Biomarkers; D053061:Herpes Zoster Vaccine
causal inference; correlate of immunity; immune correlate of protection; principal stratification; signature of protection; statistical analysis; surrogate endpoint; vaccine efficacy trial