Long-term effectiveness of live zoster vaccine against herpes zoster and related complications: a nationwide emulated target trial in South Korea

Abstract

Background: The live attenuated zoster vaccine is used to prevent herpes zoster in older individuals, but evidence on its durability remains limited, particularly across diverse populations and healthcare systems. We therefore assessed the long-term vaccine effectiveness of live attenuated zoster vaccine against herpes zoster and its complications in a nationally representative cohort of older individuals in South Korea.

Methods: We emulated target trial from a large-scale, population-based nationwide cohort of individuals aged ≥50 years in South Korea (n = 2,519,582), integrating health insurance data (Korea Health Insurance Review and Assessment Service), national health screening (Korean National Health Insurance Service), and live attenuated zoster vaccination data (Korea Disease Control and Prevention Agency). Exposure was defined as receiving the live attenuated zoster vaccine between January 1, 2012, and December 31, 2021, with a follow-up period through January 31, 2024. Outcomes included incident herpes zoster, postherpetic neuralgia, herpes zoster encephalitis, and hospital admission for herpes zoster. The effectiveness and durability were estimated using adjusted hazard ratios (aHRs) with 95 % confidence intervals (CIs) from Cox proportional hazard models and restricted mean survival time (RMST) up to 10 years in an overlap-weighted cohort.

Results: Among 910,602 individuals (mean age, 61.48 [SD, 2.53] years; 47.30 % males) after overlap weighting, vaccination was associated with significantly lower risks of herpes zoster (aHR, 0.48 [95 % CI 0.48-0.49]; RMST differences, 151.1 days), postherpetic neuralgia (0.47 [0.46-0.48]; 86.0 days), herpes zoster encephalitis (0.40 [0.25-0.63]; 0.20 days), and hospital admission for herpes zoster (0.33 [0.31-0.35]; 14.1 days). Although effectiveness declined, protection remained significant for up to 8 years. Similar waning patterns were observed for postherpetic neuralgia and hospital admissions. Greater effectiveness was observed in males, individuals aged <60 years, and those who consumed alcohol less than once per week.

Conclusion: Live attenuated zoster vaccination was associated with substantially reduced risks of herpes zoster and its complications in South Korea. Despite waning, protection persisted for 8 years, supporting the continued role of live attenuated zoster vaccine, particularly where recombinant vaccines are limited.

Keywords: Herpes zoster; Live zoster vaccine; Long-term effectiveness; Vaccine effectiveness.