VARICELLA-ZOSTER VIRUS (VZV)-SPECIFIC CELL-MEDIATED IMMUNITY MEASURED BY RESPONDER CELL FREQUENCY AND ELISPOT ASSAY IN ELDERLY SUBJECTS RECEIVING MULTIPLE DOSES OF A VZV VACCINE

*M.J. Levin (1), J.G. Smith (3), M. Bernard (1), A.R. Hayward (2), C. Chan (3), I. Chan (3), B. Wang (3), R. Vessey (3) & M.J. Caulfield (3) (1)Departments of Pediatrics, Infectious Diseases; (2)Pediatrics, Allergy and Immunology, University of Colorado School of Medicine, Denver, Colorado; (3)Merck Research Laboratories, West Point, Pennsylvania

This study evaluated the safety, tolerability and immunogenicity of a booster dose of a live attenuated varicella-zoster virus (VZV) vaccine in healthy subjects > 60 years of age who had received one or two doses of a VZV vaccine more than 5 years previously. One hundred ninety seven subjects were enrolled in the study. This booster dose was well tolerated and no vaccine related serious adverse events were reported. Cell mediated immunity (CMI) to VZV was evaluated before and 6 weeks after the booster vaccination by both a limiting dilution responder cell frequency (RCF) assay and a novel interferon-y ELISPOT assay. Pre-vaccination VZV-specific CMI as measured by ELISPOT varied widely but tended to be lower in older individuals. Preliminary analysis indicates that vaccination resulted in a detectable increase in VZV-specific CMI in most subjects post-vaccination when measured by either assay. The magnitude of the vaccine-induced ELISPOT response (in terms of fold-rise) was inversely related to the pre-vaccination values. The response to vaccination was not influenced by gender or age. Recipients of two doses of live vaccine prior to the current booster dose tended to respond better than those who had previously received only one prior dose of vaccine. Comparison of the assays showed that the ELISPOT assay was more sensitive and had a wider dynamic range than the RCF assay. The results indicate that a live attenuated VZV vaccine may be safe and immunogenic in an elderly population, and that the ELISPOT assay may be a superior method for longitudinal monitoring of VZV-specific vaccine-induced immunity.

Corresponding Author: M.J. Levin, M.D., Chief, Pediatric Infectious Diseases & Professor of Pediatrics and Medicine University of Colorado Health Sciences Center, 4200 E. 9th Avenue, Box C227, Denver, CO 80262, USA