Publication date: Jul 24, 2025

To assess the effectiveness of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monovalent XBB. 1.5 variant vaccine for reducing coronavirus disease 2019 (COVID-19) mortality among people aged 65 years or older. Retrospective observational cohort study; analysis of linked 2021 Australian census, Australian Immunisation Register, and death registrations data. Australia, 1 August 2023 to 29 February 2024; dominant SARS-CoV-2 Omicron subvariants: XBB-related until early December 2023, then the BA. 2.86-related JN. 1. People aged 65 years or older on 1 August 2023. Relative vaccine effectiveness by time since most recent booster and booster type (XBB. 1.5 variant or other), adjusted for age, gender, state/territory, household income, number of medical conditions, number of general practice visits, and influenza vaccination during 2022. By 29 February 2024, 1620 COVID-19-specific deaths among 4. 12 million people aged 65 years or older had been recorded. COVID-19 mortality was lower among people who had received XBB. 1.5 COVID-19 booster doses during the preceding 90 days (21 [95% confidence interval {CI}, 9-52] per 100 000 person-years) than among those whose most recent booster had been more than 365 days ago (72 [95% CI, 61-84] per 100 000 person-years). The relative vaccine effectiveness for XBB. 1.5 boosters during the preceding 90 days (v any booster > 365 days) was 74. 7% (95% CI, 59. 9-84. 1%); for other booster types it was 51. 6% (95% CI, 39. 3-61. 4%). Relative vaccine effectiveness declined with time: for any booster during the preceding 91-180 days (v any booster > 365 days) it was 31. 2% (95% CI, 18. 9-41. 6%); for any booster during the preceding 181-365 days it was 13. 1% (95% CI, 1. 8-23. 2%). Relative XBB. 1.5 vaccine effectiveness was similar in analyses restricted to 1 December 2023 – 29 February 2024, when the dominant Omicron subvariant was JN. 1. Recent booster vaccination with the XBB. 1.5 monovalent COVID-19 vaccine was highly effective for preventing COVID-19 deaths among people aged 65 years or older, including during the period in which the JN. 1 was the dominant SARS-CoV-2 Omicron subvariant. Our findings provide support for the recommendation that people aged 65 years or older receive COVID-19 vaccine booster doses every six months.

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