A Double-Blind, Randomized, Controlled, Multicenter Safety and Immunogenicity Study of a Refrigerator-Stable Formulation of Zostavax

Abstract

ABSTRACT The vaccine Zostavax has been shown to prevent herpes zoster (HZ) and postherpetic neuralgia and is recommended for individuals ≥60 years of age. This study compared the safety and the immunogenicity of a refrigerator-stable formulation (Zostavax refrigerated) with those of the current formulation (Zostavax frozen) in subjects ≥50 years of age. Subjects with a negative history for HZ were randomized 1:1 to receive one dose of either formulation. Enrollment was stratified 1:2 by age (50 to 59 years and ≥60 years). Safety was evaluated for 28 days postvaccination. Varicella-zoster virus (VZV) antibody responses were measured by a glycoprotein enzyme-linked immunosorbent assay (gpELISA). The primary endpoints were the VZV antibody geometric mean titer (GMT; day 28), the VZV antibody geometric mean rise (GMR; days 1 to 28), and the incidence of vaccine-related serious adverse experiences (AEs) over 28 days. The refrigerated ( n = 182) and frozen ( n = 185) formulations induced similar GMTs (727.4 and 834.4 gpELISA units/ml, respectively); the estimated GMT ratio (refrigerated formulation/frozen formulation) was 0.87 (95% confidence interval, 0.71 to 1.07). The GMRs were 2.6- and 2.9-fold, respectively. No vaccine-related serious AEs were reported in either group, and the safety profiles of the formulations were generally similar. The frequencies of injection-site AEs during follow-up were 35.6% and 46.4% in the refrigerated and the frozen formulation groups, respectively, and were generally mild. The frequencies of systemic AEs were similar in the two groups, and those of vaccine-related AEs were ∼6% in both groups. The refrigerator-stable formulation of Zostavax has an acceptable safety profile and is as immunogenic as the frozen formulation; thus, the vaccine may be used in clinical settings where freezer availability is limited.