ObjectiveTo estimate the protection of COVID-19 vaccine boosters against mild/asymptomatic and moderate SARS-CoV-2 infection over a 6-month period of XBB.1.5 and JN.1 variant circulation.DesignMulti-state model applied to cohort study, adjusted for vaccination, prior infection, and demographic covariates.SettingNational Health Services (NHS) hospitals in the UK.ParticipantsHealthcare worker cohort including 2,867 eligible people with >6 months since a previous booster who tested fortnightly for SARS-CoV-2 between October 2023 and March 2024 and completed symptoms questionnaires.Main outcome measuresVaccine effectiveness (VE) of vaccine boosters received in October 2023 (baseline: booster >6 months prior), and durability of protection from a recent (past 6 months) previous infection (baseline: last infection >2 years prior) against mild/asymptomatic and moderate SARS-CoV-2 infection. Mild symptoms included acute respiratory symptoms for <5 days, moderate symptoms included influenza-like illness, acute respiratory symptoms for 5+ days, or sick-leave. VE and acquired protection were estimated from the multi-state model as: 1 - adjusted hazard ratio.InterventionsReceipt of a COVID-19 bivalent original/BA.4-5 or monovalent XBB.1.5 booster during October 2023.ResultsHalf of eligible participants (1,422) received a booster during October 2023 (280 bivalent, 1,142 monovalent) and 536 (19%) had at least one PCR-confirmed infection over the study period. For the monovalent booster, VE against infection was 44.2% (95% confidence interval 21.7 to 60.3%) at 0-2 months, and 24.1% (-0.7 to 42.9%) at 2-4 months post-vaccination, with no evidence of protection by 4-6 months. For the bivalent booster, VE against infection was 15.1% (-55.4 to 53.6%) at 0-2 months and 4.2% (-46.4 to 37.3%) at 2-4 months. VE (monovalent or bivalent) against moderate infection was 39.7% (19.9 to 54.6%), and against mild/asymptomatic infection was 14.0% (-12.1 to 34.0%). Controlling for vaccination, compared to those with an infection >2 years prior, infection within the past 6 months was associated with 58.6% (30.3 to 75.4%) increased protection against moderate infection, and 38.5% (5.8 to 59.8%) increased protection against mild/asymptomatic infection.ConclusionsMonovalent XBB.1.5 boosters provided short-term protection against SARS-CoV-2 infection, particularly against moderate symptoms. Vaccine formulations which target the circulating variant may be suitable for inclusion in seasonal vaccination campaigns among healthcare workers.