Safety of Zoster Vaccine in Elderly Adults Following Documented Herpes Zoster

A large randomized double-blind placebo-controlled clinical trial, Department of Veterans Affairs Cooperative Study Program (VA CSP) Number 403: the Shingles Prevention Study (SPS), conducted in 38 546 ambulatory immunocompetent adults ≥60 years of age, demonstrated that a live attenuated Oka/Merck varicella zoster virus (VZV) vaccine (hereafter, “zoster vaccine”) reduced the burden of illness due to herpes zoster (HZ)–related pain and/or discomfort by 61%, the incidence of postherpetic neuralgia by 67%, and the incidence of HZ by 51% [1]. Vaccine efficacy is thought to result from a vaccine-induced increase in VZV-specific cell-mediated immunity [2–4]. Zoster vaccine (Zostavax, Merck Sharp & Dohme) was licensed by the US Food and Drug Administration in 2006 for the prevention of HZ in immunocompetent adults ≥60 years of age, and is recommended by the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices for routine administration to eligible adults ≥60 years of age, regardless of a prior history of HZ [5, 6]. The rationale for administration of zoster vaccine irrespective of prior HZ includes the (1) questionable reliability of a self-reported history of HZ, (2) assumption that prior HZ will not increase the incidence or severity of adverse events associated with administration of zoster vaccine, and (3) lack of knowledge regarding the level and duration of protection induced by an episode of HZ. Data from the SPS indicate that increased levels of VZV-specific cell-mediated immunity induced by zoster vaccine or HZ often decline significantly to near baseline levels within 3 years after vaccination or HZ [3, 4]. Because subjects with prior HZ were excluded from the SPS, there is little direct evidence of the safety of zoster vaccine in subjects with prior HZ. A small study comparing zoster vaccine to placebo in 101 adults ≥50 years of age, all with a history of HZ ≥5 years prior to vaccination, indicated that the vaccine was well tolerated and boosted titers of VZV antibody [7]. Beginning in 2005, SPS participants who had received placebo and could be contacted were offered zoster vaccine without charge, in accordance with the SPS protocol [1]. Because 420 of the 13 681 placebo recipients who received zoster vaccine had experienced an episode of documented HZ during the SPS, we compared the safety of zoster vaccine in these 420 subjects with documented HZ to the safety of zoster vaccine in the 13 261 SPS placebo recipients who had never experienced HZ.