Herpes zoster vaccine live: A 10 year review of post-marketing safety experience

Abstract

Background Zoster vaccine is a single dose live, attenuated vaccine (ZVL) indicated for individuals ≥50 years-old for the prevention of herpes zoster (HZ). Safety data from clinical trials and post-licensure studies provided reassurance that ZVL is generally safe and well tolerated. The objective of this review was to provide worldwide post-marketing safety information following 10 years of use and >34 million doses distributed. Methods All post-marketing adverse experience (AE) reports received worldwide between 02-May-2006 and 01-May-2016 from healthcare professionals following vaccination with ZVL and submitted to the MSD AE global safety database, were analyzed. Results A total of 23,556 AE reports, 93% non-serious, were reported. Local injection site reactions (ISRs), with a median time-to-onset of 2 days, were the most frequently reported AEs followed by HZ. The majority of HZ reports were reported within 2 weeks of vaccination and considered, based on time-to-onset, pathogenesis of HZ, and data from clinical trials, to be caused by wild-type varicella-zoster virus (VZV). HZ confirmed by PCR analysis to be VZV Oka/Merck vaccine-strain was identified in an immunocompetent individual 8 months postvaccination and in 4 immunocompromised individuals. Disseminated HZ was reported very rarely (<1%) with 38% occurring in immunocompromised individuals. All reports of disseminated HZ confirmed by PCR as VZV Oka/Merck vaccine-strain were in individuals with immunosuppressive conditions and/or therapy at the time of vaccination. Conclusions The safety profile of ZVL, following 10 years of post-marketing use, was favorable and consistent with that observed in clinical trials and post-licensure studies.

Effect of Recombinant Zoster Vaccine on Incidence of Herpes Zoster After Autologous Stem Cell Transplantation

“…6,7 Vaccination has the potential to provide long-term protection against herpes zoster, but live attenuated vaccines are contraindicated in immunocompromised individuals because of the risk of varicella resulting from spread of the vaccine strain. 8,9 An adjuvanted recombinant zoster vaccine, consisting of the varicella-zoster virus glycoprotein E antigen and the AS01 B adjuvant system, is nonlive and has no associated risk of triggering the infection in healthy adults. 10 This vaccine significantly reduced herpes zoster risk in adults aged at least 50 and at least 70 years (vaccine efficacy, 91%) and has been licensed in several countries.…”

T Lymphocytes as Measurable Targets of Protection and Vaccination Against Viral Disorders

“…The single dose, lyophilized, live, attenuated VZV vaccine (i.e., zoster vaccine live (Zvl), Zostavax, Merck) is indicated for prevention of latent VZV reactivation leading to shingles in individuals older than 50 years. ZVL is licensed in over 55 countries, with 34 million distributed doses globally (Willis et al, 2017), and which has associated efficacy rates of over 50% in all ages tested (Oxman et al, 2005;Schmader et al, 2012); consistent with original clinical trial datasets (Tseng et al, 2011;Langan et al, 2013;Marin et al, 2015). However, increases in VZV susceptibility have arisen due to increasing aging populations, and in immune-suppressed organ transplant recipients, chemotherapy patients, HIV-infected individuals, and those suffering from chronic illnesses (Forbes et al, 2014).…”

Author reply

“…8 Analysis of all worldwide post-marketing adverse events (2006-2016) following ZVL found that disseminated HZ was reported in <1% of cases. 9 This suggests that while such an event can occur, it is uncommon. Given the significant morbidity seen with HZ, 10 we would suggest the benefit of ZVL, even in the setting of LFN is worth the riskafter discussion with the patient regarding the benefit/risk ratio.…”

“…8 While most of the 4826 patients who were immunosuppressed around the time of ZVL had only low-dose prednisone, 126 of them were taking LFN. 9 This suggests that while such an event can occur, it is uncommon. 9 This suggests that while such an event can occur, it is uncommon.…”