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Federica Brosio,1 Giulia Masetti,1 Giulio Matteo,1 Armando Stefanati,2 Giovanni Gabutti2 1Postgraduate School of Hygiene and Preventive Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, Italy; 2Department of Medical Sciences, University of Ferrara, Ferrara, Italy Abstract: Herpes zoster (HZ) is an acute vesicular dermatitis with a typical dermatomal distribution, caused by the varicella zoster virus (VZV), often preceded and accompanied by prodromal pain or pruritus. HZ may be related to several complications such as postherpetic neuralgia (PHN). The incidence and severity of the disease increase with aging, due to immunosenescence and in particular to the decline of the specific cell-mediated immunity (CMI). The impact of HZ in terms of morbidity and short- and long-term complications, the availability of suboptimal treatment options to date, and the high costs for the diagnostic and clinical-therapeutic management of patients have motivated the search for a new preventive approach through the development of a vaccine. The vaccine currently in use with live-attenuated virus (ZVL) has been shown to be effective in reducing the incidence of HZ, its impact, and the onset of PHN, although the efficacy is lower in older subjects and tends to decrease some years after immunization. A new adjuvanted recombinant subunit vaccine (HZ/su), containing the VZV glycoprotein E (gE) and the AS01B adjuvant system, is now a very promising alternative to ZVL; in several clinical studies, it showed a good safety profile and was able to elicit high immune humoral and cell-mediated responses, both maintained up to 9 years. Furthermore, HZ/su vaccine was effective both in preventing HZ and in reducing the onset of PHN and other complications. HZ/su has been recommended and preferred over ZVL by the Advisory Committee on Immunization Practices (ACIP) for the prevention of HZ and its complications in immunocompetent adults aged ≥50 years, even if already vaccinated with ZVL, through a two-dose schedule. HZ/su has been approved in Canada, USA, Europe, and Japan and is currently being approved in Australia. The aim of this review was to describe the epidemiological data, HZ and PHN risks and their impact on the social life and common life of infected people, and ZVL and HZ/su vaccine development including various clinical trials and efficacy, safety, and tolerability profiles. Keywords: herpes zoster, adjuvanted recombinant herpes zoster subunit vaccine, live-attenuated herpes zoster vaccine