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

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. Herpes zoster (HZ), also known as shingles, is an often serious condition associated with the reactivation of varicellazoster virus (VZV) in individuals who have been exposed to the virus earlier in life (11, 12). After the initial infection, which manifests clinically as chickenpox, VZV can become latent and reside in the dorsal or cranial nerve ganglia. The reactivation of VZV as HZ is usually characterized by a unilateral, dermatomally distributed cutaneous rash.