This study investigated the vaccine effectiveness (VE) of the Omicron JN.1 COVID-19 vaccine against infection with SARS-CoV-2 JN.1-derived subvariants in the Netherlands. The evaluation period spanned from September 23, 2024, to February 23, 2025. The objective was to quantify how well the JN.1 vaccine protected against infections caused by the virus and its subvariants in a real-world, prospective cohort setting.
Participants were enrolled in the ongoing Vaccine Study COVID-19 (VASCO), which is a prospective cohort study. Eligibility for JN.1 vaccination included individuals aged 60 years or older, as well as those under 60 years with underlying medical risk conditions or who were healthcare workers.
Data were collected periodically through questionnaires and serology measurements. Participants were provided with self-testing kits to detect SARS-CoV-2 infection through antigen tests. This comprehensive surveillance approach enabled frequent and timely detection of infections and contributed data on vaccine impact.
SARS-CoV-2 infection was defined by either a positive self-administered test reported by participants or detection of anti-nucleoprotein antibodies indicative of recent infection. To determine the infecting variant, viral genetic material from positive self-tests was subjected to whole genome sequencing.
This allowed the differentiation between infections caused by the primary JN.1 variant and its subvariants KP.3.1.1 and XEC, facilitating subvariant-specific vaccine effectiveness estimates.
Overall vaccine effectiveness against SARS-CoV-2 infection was estimated using Cox proportional hazards regression models incorporating vaccination status as a time-varying exposure.
For subvariant-specific VE against KP.3.1.1 and XEC, a multinomial logistic regression was applied. This analysis matched infected and uninfected individuals by calendar week to control for temporal changes in infection exposure.
All models were adjusted for key covariates including age group, sex, level of education, presence of medical risk conditions, and history of prior SARS-CoV-2 infection to reduce confounding.
The study included 4,490 vaccine-eligible participants under 60 years of age, of whom 29% had received the JN.1 vaccine. Additionally, there were 19,349 participants aged 60 years or above, with 74% vaccinated.
This vaccination distribution reflects targeted vaccine uptake among higher-risk older adults compared to younger adults with risk factors.
During the 5-month follow-up period characterized by relatively low SARS-CoV-2 incidence, 2,142 infections were recorded among cohort members. The majority (72%) were identified through self-reported positive tests.
In participants younger than 60 years, the JN.1 vaccine was associated with a VE of 16% (95% confidence interval [CI]: -11% to 36%) against SARS-CoV-2 infection. For those aged 60 years or older, VE was slightly lower, estimated at 13% (95% CI: 2% to 23%). These VE estimates indicate modest protection against infection.
Of the infections analyzed, 251 (27%) were identified as caused by the KP.3.1.1 subvariant, and 195 (5%) were due to the XEC subvariant.
The vaccine effectiveness against KP.3.1.1 did not significantly differ from VE against XEC, with an odds ratio of 1.3 (95% CI: 0.8 to 2.1). However, point estimates suggest potentially lower VE against the XEC subvariant. Statistical power was limited for detecting significant differences.
In summary, the Omicron JN.1 vaccination provided limited additional protection against SARS-CoV-2 infection during the study period among high-risk and older adults in the Netherlands. Protection appeared modest and did not differ significantly between JN.1-derived subvariants KP.3.1.1 and XEC.
Findings emphasize the challenges in achieving high effectiveness against infection with emerging Omicron subvariants and highlight the need for ongoing surveillance and vaccine optimization strategies.