Strain-specific anti-RBD IgG antibody titers against the WT, XBB.1.5, JN.1, and KP.3 strains consistently correlate with neutralizing activity following SARS-CoV-2 XBB.1.5-adapted mRNA vaccination

Introduction Data on the correlation between SARS-CoV-2 neutralizing activity and strain-specific anti-RBD IgG antibody (anti-RBD) titers is limited, particularly in the context of XBB.1.5-adapted vaccination. Methods A direct comparison of neutralizing activity, measured as 50% neutralization (NT 50 ), and anti-RBD titers, measured using an ELISA, was conducted using serum samples collected in Japan before and after XBB.1.5-adapted mRNA vaccination. Results A total of 108 serum samples from 54 patients were analyzed. A strong correlation between neutralizing activity and anti-RBD titers was observed for the wild-type (WT), XBB.1.5, JN.1, and KP.3 strains (r = 0.94, 0.87, 0.86, and 0.82, respectively). This correlation persisted when stratifying pre- and post-vaccination samples (r = 0.92, 0.83, 0.85, and 0.82, respectively, for pre-vaccination samples and r=0.96, 0.85, 0.82, and 0.75, respectively, for post-vaccination samples). Both NT 50 and anti-RBD titers significantly increased against all four tested strains after vaccination ( p < 0.001), with the highest fold change observed for the XBB.1.5 variant. Additionally, variant specificity, defined as the ratio of variant to WT values, significantly increased for XBB.1.5, JN.1, and KP.3 after vaccination in NT 50 and was also observed in anti-RBD titers. Conclusions These findings, demonstrating a strong correlation with neutralizing activity not only against the WT strain but also against the XBB.1.5, JN.1, and KP.3 variants, suggest that strain-specific anti-RBD IgG antibody titers would be useful as an indicator of humoral immunity following XBB.1.5-adapted vaccination.