Comparable Neutralizing Antibody Responses Following JN.1 and KP.2‐Based COVID‐19 Vaccination Suggest Limited Added Value of Minor Strain Updates: A Multicentre Immunogenicity Study

OBJECTIVES: COVID-19 vaccines are periodically updated to address SARS-CoV-2 evolution. Whether minor antigen changes provide immunological or even clinical benefit remains unclear. This study compared neutralizing antibody responses following vaccination with the JN.1-based or KP.2-based 2024/25 Pfizer-BioNTech mRNA vaccine. METHODS: Adults aged 18-64 years who received the JN.1 vaccine in Austria, or the KP.2 vaccine in the United States were enrolled. A single blood sample was obtained within 120 days post-vaccination. Pseudovirus neutralization assays against SARS-CoV-2 variants XBB.1.5, JN.1, KP.2, KP3.1.1, XEC and LP.8.1 were performed. Geometric mean titre (GMT) ratios were analysed using t-tests and multivariable regression adjusted for age, sex, vaccination intervals, and prior infection. RESULTS: Among 191 participants (78 JN.1, 113 KP.2), GMTs (95% CI) for XBB.1.5 variant were higher in the JN.1 cohort (3498 [2535-4826]) than in the KP.2 cohort (1901 [1386-2607]), GMT ratio 1.84 (1.16-2.92). For the JN.1 variant, GMTs were 1122 (819-1538) in the JN.1 cohort and 695 (510-948) in the KP.2 cohort (GMT ratio: 1.61 [1.03-2.54]). GMTs for other variants did not differ significantly. After adjustment, only the XBB.1.5 difference remained significant (p = 0.04). CONCLUSIONS: Comparable neutralizing responses across JN.1 lineage variants suggest that annual COVID-19 strain updates targeting variants with small differences within the same antigenic cluster may have limited impact on vaccine-induced protection. These findings may inform future public health policy and regulatory decision-making for COVID-19 vaccines.