Recombinant zoster vaccine showed about 56% effectiveness against herpes zoster in adults aged 65 years and older, with similar protection in immunocompromised (54%) and immunocompetent (56%) individuals, according to an analysis of more than 3 million Medicare beneficiaries. A second dose provided an additional nearly 68% effectiveness beyond the first dose.
In the study, published in the Annals of Internal Medicine, investigators conducted a target trial emulation study using data from a 20% random sample of fee-for-service Medicare beneficiaries covered by Parts A, B, and D between 2007 and 2019. In the analysis, they emulated 12 sequential trials beginning in January 2018, each lasting at least 12 months. The participants could enroll in multiple trials if eligible.
The investigators noted that approximately 3 million individuals were eligible for each trial. In total, the analysis included nearly 37 million observations among 3.5 million unique individuals, each of whom participated in an average of 11 trials. Vaccine effectiveness was 56% against herpes zoster, 55% against herpes zoster ophthalmicus, and 72% against postherpetic neuralgia. An estimated 698 herpes zoster cases, 58 herpes zoster ophthalmicus cases, and 78 postherpetic neuralgia cases per 100,000 persons were averted by vaccination.
Among the participants who had previously received the live zoster vaccine, the recombinant zoster vaccine effectiveness was 52% compared with 58% among those without prior live vaccine. Effectiveness was similar across age groups from 65 to 80 years but lower in those 85 years and older (44%). Black individuals showed minimal benefit (18%), though this estimate was imprecise as a result of small numbers.
A second analysis assessed the additional benefit of a second dose among 146,296 individuals who received at least one dose of the recombinant zoster vaccine in 2018. Ten emulated trials were conducted, beginning 60 days after the first dose. Receipt of a second dose conferred 68% additional effectiveness against herpes zoster compared with one dose, 67% against herpes zoster ophthalmicus, and 81% against postherpetic neuralgia. Among those receiving a second dose, the median interval from the first dose was 136 days, approximately 4.5 months.
Recombinant zoster vaccine is effective in older adults, including immunocompromised adults, and 2 doses were more effective than 1. Prior ZVL recipients should be revaccinated with RZV
The recombinant zoster vaccine was preferentially recommended over the live zoster vaccine starting in 2018. While the live zoster vaccine was effective, it was contraindicated in immunocompromised individuals and showed waning immunity after approximately 5 years. Recombinant zoster vaccine is theoretically safe and effective in immunocompromised adults, but they were systematically excluded from the two major clinical trials that established vaccine efficacy.
Each of the trials included in the study had a 1-month enrollment period during which vaccination status was assessed. The participants were followed from the start of each trial until they developed herpes zoster, experienced an administrative censoring event, or deviated from their treatment assignment. Outcomes were analyzed using weighted Fine and Gray models to account for death as a competing event.
Standardization weighting was used to control for confounding by weighting untreated individuals to reflect the covariate distribution of treated individuals. Covariates included age, sex, race, ethnicity, prior live zoster vaccine receipt, and immunocompetence status. Inverse probability of censoring weights accounted for treatment assignment deviations.
Study limitations included the restriction to Medicare beneficiaries aged 65 years and older, preventing assessment of vaccine effectiveness in younger adults for whom the vaccine is also indicated. Follow-up was limited to 2018 and 2019 because of data availability. The immunocompetence algorithm included all malignant solid tumors, which may have misclassified some individuals. The study didn't assess vaccine safety.
In May 2025, the Centers for Disease Control and Prevention issued guidance removing pregnancy as an indication for recombinant zoster vaccine, though prior guidance had recommended vaccination during pregnancy.
The study authors reported grants from the National Center for Advancing Translational Sciences and the National Institute of Allergy and Infectious Diseases.
Source: Annals of Internal Medicine