Effectiveness of Omicron JN.1 vaccination against infection with JN.1-derived SARS-CoV-2 subvariants in a prospective cohort study in the Netherlands

Introduction We estimated vaccine effectiveness (VE) of JN.1 COVID-19 vaccination against SARS-CoV-2 infection by (sub)variant between 23 September 2024 and 23 February 2025. Methods JN.1 vaccine-eligible participants of an ongoing prospective cohort study (VAccine Study COvid-19; VASCO) were included: individuals aged ≥60 years, and individuals aged <60 years with a medical risk condition or who were healthcare workers. In VASCO, questionnaire and serology data are regularly collected and self-tests are provided. SARS-CoV-2 infection was based on reported positive self-tests and/or anti-nucleoprotein serology results. The variant of infection was determined by whole genome sequencing of viral genetic material in positive self-tests. VE against infection was estimated using Cox regression with JN.1-vaccination as time-varying exposure, and VE against JN.1 subvariants KP.3.1.1 and XEC using multinomial logistic regression with matching of infected and uninfected participants by calendar week. Models were adjusted for age group, sex, education level, medical risk condition and SARS-CoV-2 infection history. Results Of 4490 JN.1-vaccine eligible participants <60 years, 1283 (29%) were vaccinated. Of 19,349 participants ≥60 years, 14,400 (74%) were vaccinated. During follow-up 2142 infections occurred, of which the majority was self-reported (72%). VE was 16% (95%CI: −11-36) in participants <60 years and 13% (95%CI: 2–23) in participants ≥60 years. VE against KP.3.1.1 ( n = 251;27%) did not differ significantly from the VE against XEC ( n = 195;5%)(OR:1.3; 0.8–2.1). Conclusion We found that, during a 5-month study period with low incidence, JN.1-vaccination provided limited added protection in preventing SARS-CoV-2 infection. The observed VE estimates indicate potentially lower protection against XEC than KP.3.1.1, but the power to detect such a difference was low.