Background. The objectives of this study were to evaluate the association between varicella-zoster virus (VZV)specific humoral and cell-mediated immunity (CMI) to herpes zoster (HZ) and protection against HZ morbidity and to compare immune responses to HZ and zoster vaccine. Methods. In 981 elderly persons who developed HZ during a zoster vaccine efficacy trial (321 vaccinees and 660 placebo recipients) and 1362 without HZ (682 vaccinees and 680 placebo recipients), CMI was measured by VZV responder cell frequency and interferon-7 enzyme-linked immunospot, and antibodies were measured by VZV enzyme-linked immunosorbent assay against affinity-purified VZV glycoproteins (gpELISA). Results. Robust VZV CMI at HZ onset correlated with reduced HZ morbidity, whereas VZV gpELISA titers did not. Three weeks after HZ onset, gpELISA titers were highest in those with more severe HZ and were slightly increased in placebo recipients (compared with zoster vaccine recipients) and in older individuals. VZV CMI responses to HZ were similar in zoster vaccine and placebo recipients and were not affected by demographic characteristics or antiviral therapy, except for responder cell frequency at HZ onset, which decreased with age. When responses to zoster vaccine and HZ could be compared, VZV CMI values were similar, but antibody titers were lower. Conclusions. Higher VZV CMI at HZ onset was associated with reduced HZ severity and less postherpetic neuralgia. Higher antibody titers were associated with increased HZ severity and occurrence of postherpetic neuralgia. HZ and zoster vaccine generated comparable VZV CMI.
Bibliographical noteFunding Information:
Cooperative Studies Program, Office of Research and Development, Department of Veterans Affairs; Merck (grant to the VA Cooperative Studies Program); National Institute of Child Health and Human Development (grants N01-HD-33162 to A.W. and N01-HD-3-3345 to M.J.L.); National Institute of Allergy and Infectious Diseases (support to multiple clinical sites, grants 1R21AI073121–01A2 and N01-AI-40029 to A.W., grant U01 AI068632 to M.J.L.); National Institute of Diabetes and Digestive and Kidney Diseases (grant U01 KD61055-03 to A.W.); Health Resources and Services Administration (grant H12HA00070 to M.J.L); National Institutes of Health (grants R01 HL079955, R01 AG026364, R01 CA 10014152, T32MH19925, P60 AG 10415, M01-RR00865, R01 AG026006-01, R01 NR009228, R01 AR049840, and R01 MH 55253 to M.R.I.); Cousins Center for Psychoneuroimmunology (M.R.I.); James R. and Jesse V. Scott Fund for Shingles Research (M.N.O.).