Neutralizing antibody responses to three XBB protein vaccines in older adults

Fig. 1. Neutralizing antibody titers before and after immunization with three XBB-containing vaccines. a–c Neutralization of D614G, BA.5, XBB.1.5, JN.1, KP.2, and KP.3 pseudoviruses by individual-matched serum obtained before or after vaccination with the trivalent XBB.1.5 vaccine (a, n = 30), bivalent Omicron XBB vaccine (b, n = 30), or tetravalent XBB.1 vaccine (c, n = 30). Sera were collected before vaccination (“before”) and 3 weeks after vaccination (“after”). Each dot represents the 50% neutralization titer (NT50) for an individual, and a line connects the NT50 values for the same individual before and after vaccination. The horizontal dotted line in the neutralization assay indicates a limit of detection of 30, with serum samples demonstrating neutralization below 30 plotted as 10. The geometric mean titers (GMTs) of the neutralizing antibodies and the percentages of individuals with NT50 values above the limit of detection are presented on top of each group. Statistical analyses were performed using a two-tailed Wilcoxon matched-pairs signed-rank test to compare neutralizing antibody titers before and after vaccination. A p-value <0.05 was considered statistically significant,…

Fig. 2. Neutralization of the SARS-CoV-2 lineage before and after immunization with three XBB-containing vaccines. a–c Comparison of SARS-CoV-2 lineage-specific neutralization titers against the indicated pseudoviruses before and after trivalent XBB.1.5 vaccine (a), bivalent Omicron XBB vaccine (b), and tetravalent XBB.1 vaccine (c) immunization. Each dot represents the 50% neutralization titer (NT50) for an individual. The horizontal dotted line in the neutralization assay indicates a limit of detection of 30, with serum samples demonstrating neutralization below 30 plotted as 10. The geometric mean titers (GMTs) of the neutralizing antibodies and the percentages of individuals with NT50 values above the limit of detection are indicated below each group. Statistical analyses were performed using a two-tailed Friedman test with a false discovery rate. A p-value <0.05 was considered statistically significant, and only significant differences are displayed in the figure, with the fold change in the GMT denoted in brackets

Fig. 3. The trivalent XBB.1.5 vaccine booster elicited increased neutralizing antibody titers. a, b Comparison of neutralizing titers against the indicated pseudoviruses in serum collected from individuals before (a) and after (b) administration of the trivalent XBB.1.5 vaccine, bivalent Omicron XBB vaccine, or tetravalent XBB.1 vaccine. Each dot represents the 50% neutralization titer (NT50) for an individual. The horizontal dotted line in the neutralization assay reflects a limit of detection of 30, with serum samples exhibiting neutralization below 30 represented as 10. The geometric mean titers (GMTs) of the neutralizing antibodies are displayed on top of each group. The bar represents the GMTs and 95% confidence intervals. The dotted line indicates the limit of detection of the NT50. Statistical analyses were performed using the Kruskal‒Wallis test with the false discovery rate method for three-group comparisons of GMTs. A p-value <0.05 was considered statistically significant, and only significant differences are displayed in the figure

Fig. 4. Neutralizing antibody responses in individuals with or without medical conditions before and after immunization with three XBB-containing vaccines. a–d Comparison of the 50% neutralization titer (NT50) against the indicated pseudoviruses in individuals with (n = 13) and without (n = 17) medical conditions before receiving the trivalent XBB.1.5 booster (a), in individuals with (n = 20) and without (n = 10) medical conditions before receiving the bivalent Omicron XBB vaccine (b), in individuals with (n = 11) and without (n = 19) medical conditions before receiving the tetravalent XBB.1 vaccine (c), and in all pooled sera (d). e–h NT50 of individuals with and without medical conditions after immunization with the trivalent XBB.1.5 booster (e), bivalent Omicron XBB vaccine (f), tetravalent XBB.1 vaccine (g), or all pooled sera after immunization (h). Each dot represents the NT50 for an individual. The horizontal dotted line in the neutralization assay reflects a limit of detection of 30, with serum samples exhibiting neutralization below 30 represented as 10. The bar represents the GMTs and 95% confidence intervals. Statistical analyses were performed using the Wilcoxon rank-sum test…

Fig. 5. Antigenic map of serum virus neutralization data. a–d Antigenic maps were constructed using the Racmacs program (1.1.4) for neutralization titers against the indicated pseudoviruses from all cohorts (a), individuals before and after receiving the trivalent XBB.1.5 vaccine (b), bivalent Omicron XBB vaccine (c), and tetravalent XBB.1 vaccine (d). The circles represent the indicated variants, whereas the squares denote individual serum samples. The x- and y-axes depict antigenic units (AUs), with each grid corresponding to a 2-fold serum dilution of the neutralization titer. One square on the grid corresponds to one AU squared. Arrows between D614G and selected variants are annotated with the distance between those variants in AUs