Evaluating the Immunogenicity, Efficacy, and Effectiveness of Recombinant Zoster Vaccine for Global Public Health Policy

Abstract

Background: Herpes zoster (HZ) is a painful neurocutaneous disease caused by the varicella-zoster virus. The recombinant zoster vaccine (RZV) is becoming increasingly incorporated into national vaccination schedules. We aimed to evaluate RZV from a global public health policy perspective. Methods: We performed a rapid review of studies evaluating the immunogenicity, efficacy, and effectiveness of RZV for protection against HZ and associated complications. We searched PubMed for English-language studies published between 7 August 2012 and 30 September 2023. Included studies reported vaccine efficacy or effectiveness against HZ and HZ-associated complications. Immunogenicity studies were included if they contributed to the understanding of RZV protection over time and/or co-administration with other vaccines. HZ outcomes were stratified by socio-demographic and clinical variables. Results: From 405 identified publications, 33 were eligible for the study. Most studies were conducted in the US (N = 12), across North America (N = 10), and Europe (N = 5), or across multiple locations across North America, Latin America, and Asia-Australia (N = 6). Vaccine efficacy against HZ in immunocompetent populations ranged between 90% and 97%, while effectiveness ranged between 71% and 86%. Protection stayed above 70% for at least 10 years, with no significant differences by age or ethnicity. Conclusions: RZV is effective in reducing the risk of HZ and its associated complications. Protection is long-lasting and the vaccine is suitable for older and immunocompromised populations. However, the decision to incorporate the vaccine into national policies depends on additional factors (e.g., cost-effectiveness), which may be difficult to characterize without an understanding of the global disease burden.

Keywords: health policy; herpes zoster; immunization; vaccine; varicella zoster virus.

Figure 1

Study flow diagram.

Figure 2

Vaccine efficacy and effectiveness against herpes zoster in immunocompetent and immunocompromised populations. Studies: Lal et al., 2015 (ZOE-50) [23], Cunningham et al., 2016 (ZOE-70 only) [24], Sun et al., 2021 (A) [36], Izurieta et al., 2021 (general immunocompromised status) [38], Sun et al., 2021 (B) [39], Bastidas et al., 2019 (hematopoietic stem cell recipients) [33], Dagnew et al., 2019 (Haematological malignancy patients) [35], Khan et al., 2022 (inflammatory bowel disease patients, 50–60 years age group, vaccine effectiveness calculated from hazard ratio) [42]. V = vaccine arm; C = control arm/unvaccinated; PYs = person-years.

Figure 3

Vaccine efficacy against herpes zoster by disease in an immunocompromised trial population, reported by Stadtmauer et al. [34]. V = vaccine arm; C = control arm/unvaccinated; PYs = person-years.

Figure 4

Vaccine efficacy and effectiveness of RZV against post-herpetic neuralgia (PHN) and herpes zoster ophthalmicus (HZO). Studies: Cunningham, 2016 [24], Izurieta, 2021 [38], Sun, 2021 (A) [36], Lu, 2021 [40]. VE = vaccine efficacy/effectiveness; V = vaccine arm; C = control arm/unvaccinated; PYs = person-years.

Figure 5

Vaccine efficacy and effectiveness against herpes zoster by age. Vaccine efficacy estimates taken from ZOE-50 study [23] for age groups 50–59 years and 60–69 years, and ZOE-50/70 for age groups 70–79 years and 80+ years [24]. Khan, 2022 vaccine effectiveness calculated from hazard ratio [42]. Other studies: Sun, 2021 (A) [36], Izurieta, 2021 [38], Sun, 2021 (B) [39].

Figure 6

Vaccine efficacy and effectiveness of RZV against herpes zoster by geographic ancestry/ethnicity. RCT results reported in Willer et al. [26], observational results from Sun, 2021 (A) [36], and Sun, 2021 (B) [39]. Confidence intervals were not reported for subgroups with no cases in vaccinated cohort. VE = vaccine efficacy/effectiveness; V = vaccine arm; C = control arm/unvaccinated; PYs = person-years.

Figure 7

Vaccine efficacy (VE) against herpes zoster in the ZOE-50/70 and ZOE-LTFU studies over time since 1 month post-second dose reported in Strezova et al. [31]. No vaccine efficacy estimate given for year 5 due to switch between studies. In ZOE-50/70, VE was estimated using placebo control as comparator. In ZOE-LTFU, VE was estimated using historic controls from ZOE-50/70 placebo arm.

Figure 8

Vaccine effectiveness against herpes zoster in populations who had and had not previously been vaccinated with Zoster Vaccine Live (ZVL, Zostavax). Studies: Sun, 2021 (A) [36], Izurieta, 2021 [38]. V = vaccine arm; C = control arm/unvaccinated; PYs = person-years.