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 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Institutional Review Board of Cleveland Clinic gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors