Effectiveness of the 2023-2024 Formulation of the Coronavirus Disease 2019 mRNA Vaccine against the JN.1 Variant

Background The purpose of this study was to evaluate whether the 2023-2024 formulation of the COVID-19 mRNA vaccine protects against COVID-19 caused by the JN.1 lineage of SARS-CoV-2. Methods Employees of Cleveland Clinic in employment when the JN.1 lineage of SARS-CoV2 became the dominant circulating strain, were included. Cumulative incidence of COVID-19 was examined prospectively. Protection provided by vaccination (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression. The analysis was adjusted for the propensity to get tested, age, sex, pandemic phase when the last prior COVID-19 episode occurred, and the number of prior vaccine doses. Results Among 47561 employees, COVID-19 occurred in 838 (1.8%) during the 16-week study period. In multivariable analysis, the 2023-2024 formula vaccinated state was associated with a significantly lower risk of COVID-19 while the JN.1 lineage was the dominant circulating strain (hazard ratio [HR], .77; 95% confidence interval [C.I.], .62-.94; P = .01), yielding an estimated vaccine effectiveness of 23% (95% C.I., 6%-38%). Compared to 0 or 1 prior vaccine doses, risk of COVID-19 was incrementally higher with 2 prior doses (HR, 1.46; 95% C.I., 1.12-1.90; P < .005), 3 prior doses (HR, 1.95; 95% C.I., 1.51-2.52; P < .001), and more than 3 prior doses (HR, 2.51; 95% C.I., 1.91-3.31; P < .001). Conclusions The 2023-2024 formula COVID-19 vaccine given to working-aged adults afforded a low level of protection against the JN.1 lineage of SARS-CoV-2, but a higher number of prior vaccine doses was associated with a higher risk of COVID-19. Summary Among 47561 working-aged Cleveland Clinic employees, the 2023-2024 formula COVID-19 vaccine was 23% effective against the JN.1 lineage of SARS-CoV-2, but a higher number of prior COVID-19 vaccine doses was associated with a higher risk of COVID-19.