The research team, led by Joanne Reekie and Bette Liu, exploited Australia’s extraordinary national data infrastructure to answer two linked questions: whether the country’s zoster vaccination program actually reduced disease at the population level, and how well the current recombinant zoster vaccine protects the people it targets. Using the Person Level Integrated Data Asset managed by the Australian Bureau of Statistics, the investigators linked records from the Australian Immunisation Register, the Pharmaceutical Benefits Scheme, the Medicare Benefits Schedule and death registrations, with data available through 30 June 2025. Because zoster diagnoses are not captured directly in these registries, the team used dispensed prescriptions for antiviral drugs specifically indicated for zoster treatment, including aciclovir, valaciclovir and famciclovir, as a surrogate marker of disease.

The ecological arm of the study tracked quarterly antiviral prescription rates across the adult population from January 2014 to June 2025, spanning the entire history of Australia’s national zoster vaccination effort. That effort began in November 2016 with a single dose of the live-attenuated zoster vaccine, known by the brand name Zostavax, offered to people aged 70 with catch-up for those aged 71 to 79. The live vaccine was never an option for immunocompromised people because it contains a weakened but living virus. In June 2021 the adjuvanted recombinant zoster vaccine, Shingrix, became available in Australia, and in November 2023 it replaced the live vaccine on the National Immunisation Program, with free eligibility extended to everyone aged 65 and over and to adults aged 18 to 64 taking selected immunocompromising medications.

The prescription data told a striking temporal story. Rates of zoster antiviral dispensing among 70 to 79 year olds fell from 3.84 per 1000 population in the final quarter of 2016 to 2.61 per 1000 by early 2018, coinciding with the introduction of the live vaccine. After the recombinant vaccine joined the national program in late 2023, declines appeared in every eligible age group: rates in 65 to 69 year olds fell from 3.16 to 2.32 per 1000, in 70 to 79 year olds from 3.07 to 2.30 per 1000, and in those aged 80 and over from 3.79 to 2.81 per 1000 by mid-2025. Crucially, prescription rates among adults aged 18 to 64 remained essentially stable across the entire eleven-year observation window, a pattern consistent with the declines being driven by vaccination of the targeted older groups rather than by some population-wide shift.

Not every trend mapped neatly onto program milestones. Between late 2021 and mid-2023, prescription rates declined across all age groups, a period that corresponds to no change in zoster vaccination policy and to only limited private uptake of the newly available recombinant vaccine. The authors suggest the COVID-19 pandemic and reduced healthcare-seeking behaviour during that period as a plausible explanation. Rates in younger adults returned to pre-2021 levels by late 2023, while rates in those aged 65 and over continued downward, a divergence that aligns with the expanded recombinant vaccine eligibility. The data also carry a reassuring message about childhood chickenpox vaccination: despite hypotheses that reduced natural boosting with wild-type varicella might raise adult zoster risk, prescription rates among 18 to 49 year olds stayed low and stable throughout the study period.

To measure vaccine effectiveness directly, the team constructed two cohorts. The first comprised 4,488,937 adults aged 65 and over on 1 November 2023, the day the recombinant vaccine entered the national program. Most, 64.6 percent, had no record of zoster vaccination at baseline, while a third had received the older live vaccine, mostly those aged 70 and above who had been eligible under the earlier program. During a median follow-up of 607 days, 71,985 individuals, or 1.6 percent of the cohort, had a record of zoster antiviral treatment. Uptake of the new vaccine was substantial but incomplete: among those without prior recombinant vaccination, 42 percent received at least one dose during follow-up, and 35 percent completed the two-dose series by 30 June 2025, with a median interval of 98 days between doses.

The effectiveness estimates in this older cohort were solid. The incidence rate of zoster was 12.84 per 1000 person-years among unvaccinated individuals, compared with 4.94 per 1000 person-years among those who had received two doses of the recombinant vaccine. After adjustment for age, gender, general practitioner visit frequency, comorbidities, prior zoster treatment and immunocompromising medication use, two-dose effectiveness against treated zoster was 63 percent, with a single dose providing 54 percent. The older live vaccine performed considerably worse: 37 percent when given within the previous five years and only 20 percent when given more than five years earlier, a waning pattern that mirrors international evidence and underpins the global phase-out of the live vaccine. Effectiveness of the recombinant vaccine was consistent across the 65 to 69, 70 to 79 and 80-plus age strata, and rose slightly to 69 percent in a subgroup analysis restricted to people with no prior zoster diagnosis.

The second cohort examined 239,002 adults aged 18 and over who were immunocompromised by virtue of taking selected immunomodulatory or immunosuppressive medications for at least two consecutive months, ranging from moderately to highly immunocompromising therapies. This group fared distinctly worse on both counts. More than 80 percent were unvaccinated at baseline, and by the end of follow-up only 22 percent had completed two recombinant vaccine doses, though the figure concealed a sharp age divide: 44 percent among those 65 and over, who were eligible for free vaccination regardless, versus just 10 percent among those aged 18 to 64, whose eligibility for the moderately immunocompromising categories only opened in September 2024. Overall zoster incidence in this cohort was 17.59 per 1000 person-years, and two-dose effectiveness was 43 percent, with one-dose effectiveness of 36 percent and the live vaccine providing a mere 16 percent.

Most striking was the age gradient within the immunocompromised cohort. Two-dose effectiveness was 48 percent among those aged 65 and over but only 22 percent, with a confidence interval approaching zero, among those aged 18 to 64. The authors offer several non-exclusive explanations. Younger immunocompromised patients may genuinely mount weaker vaccine responses because they receive more potent immunosuppressive regimens; the study found that 41 percent of immunocompromising medications dispensed to the younger group were classified as highly immunocompromising, compared with 31 percent in the older group. Alternatively, the surrogate outcome may perform differently across ages, since previous Australian research suggests general practitioners are less likely to prescribe zoster antivirals to younger patients, which could dilute the measured signal. The 43 percent estimate also sits below the roughly 60 percent efficacy reported in trials that focused on narrower immunocompromised populations such as transplant recipients and people with haematological malignancy, underscoring the value of studying a broad, heterogeneous medicated population.

The authors are candid about the limitations inherent in registry-based surveillance. Vaccination reporting to the Australian Immunisation Register only became mandatory in 2021, so some live-vaccine recipients may have been misclassified as unvaccinated, biasing effectiveness estimates downward. The antiviral prescription outcome may capture suspected as well as confirmed zoster, and milder cases that went untreated would have been missed entirely, both of which would push estimates toward the null. The ecological trends, while compelling, are not a direct measure of incidence because repeat prescriptions across different months were counted again. Even so, the convergence of two independent analytical approaches, population-level prescription declines timed to program changes and cohort-based effectiveness estimates, provides mutually reinforcing evidence that targeted zoster vaccination is working. The clear message for policy is twofold: the recombinant vaccine delivers meaningful protection to older adults, but immunocompromised people, who face the highest risks, receive weaker protection and are vaccinated at suboptimal rates, demanding greater provider awareness, stronger uptake efforts and continued monitoring of how long protection lasts in this vulnerable group.

Subject of Research: Population-based evaluation of herpes zoster vaccine impact and effectiveness in older and pharmacologically immunocompromised adults in Australia

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

Article References: Reekie, J., Stepien, S., Li-Kim-Moy, J., Simpson, A., Macartney, K., & Liu, B. (2026). The epidemiological impact and effectiveness of herpes zoster vaccination among older and pharmacologically immunocompromised adults: a population-based observational study. The Lancet Regional Health – Western Pacific, 74, Article 101982. https://doi.org/10.1016/j.lanwpc.2026.101982

Image Credits: AI Generated

DOI: 10.1016/j.lanwpc.2026.101982

Keywords: herpes zoster, shingles, recombinant zoster vaccine, Shingrix, vaccine effectiveness, immunocompromised, older adults, Australia, National Immunisation Program, postherpetic neuralgia, varicella zoster virus, pharmacoepidemiology