The epidemiological impact and effectiveness of herpes zoster vaccination among older and pharmacologically immunocompromised adults: a population-based observational study

BACKGROUND: Australia used the live attenuated herpes zoster vaccine (ZVL, Zostavax®) for 70-79 year-old adults in its National Immunisation Program from 2016. In November 2023 this was replaced with the recombinant adjuvanted herpes zoster vaccine (RZV, Shingrix) and eligibility expanded to include adults ≥65 years old and immunocompromised adults ≥18 years. We aimed to assess the vaccine program impact and RZV effectiveness in eligible adults. METHODS: Using linked national immunisation registry and zoster-specific antiviral prescription data as a proxy outcome, patterns of antiviral use from 2014 to 2025 were assessed in an ecological study. A separate vaccine effectiveness (VE) study estimated VE using multivariable Cox-regression hazards models with time-varying vaccine exposure in 4,488,937 individuals aged ≥65 years (65+ cohort) and 239,002 adults aged ≥18 years who were immunocompromised due to medication use (pharmacologically immunocompromised cohort). VE was estimated using the formula VE = (1-hazard ratio) × 100%. FINDINGS: Declines in zoster-specific antiviral prescriptions temporally coincided with vaccine program changes between 2014 and 2025. During November 2023-June 2025, herpes zoster incidence in the 65+ years and the pharmacologically immunocompromised cohorts were 9.99 and 17.59 per 1000 person-years respectively. By 30th June 2025, 35% (N = 1,569,950) of the 65+ cohort and 22% (N = 51,455) of the pharmacologically immunocompromised cohort had received 2 doses of RZV. Comparing 2 doses of RZV to those not vaccinated in the 65+ years cohort, 2 dose VE was 63% (95% CI: 62%, 64%), with similar estimates across age groups (65-69, 70-79, and 80+ years). Among the pharmacologically immunocompromised adults VE was 43% (95% CI: 38%, 49%). INTERPRETATION: RZV demonstrated good protection against zoster in older adults, with lower effectiveness in the pharmacologically immunocompromised population. Vaccine uptake in both cohorts was suboptimal. Improving vaccine coverage and ongoing evaluation of effectiveness over extended durations is needed, particularly in the immunocompromised population. FUNDING: This work was funded by the Australian Government Department of Health, Disability and Ageing.