Figure 1.

Hybrid immunity is associated with increased and more stable cross-variant neutralization responses

(A) Schematic representation of plasma samples collection from individuals previously infected or not who received 2 doses of mRNA vaccine were tested for neutralization activity against pseudo viruses expressing the WH1, B.1.217.2 (Delta), BA.1, BA.2, and BA.4/5 SARS-CoV-2 Spike proteins. Plasma samples were collected at about 1 or 6 months after last vaccination.

(B) Raw ID₅₀ (reciprocal dilutions) titers against the indicated variant Spikes. Horizontal bars and numbers indicate ID₅₀ geometric means (GMT) for each group and error bars indicate 95% confidence intervals. At the bottom are fold changes for the indicated comparisons. For the comparison between 1- and 6-month plasma samples (intragroup), we applied a Wilcoxon paired test or a Prentice Z test when undetectable titers were observed. For intergroup comparison we applied a Mann-Whitney test or a Peto-Peto test when undetectable titers were observed. Significant p values are indicated and were corrected for multiple comparison (∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001). Dashed lines indicate the assay lower limit of detection (60 reciprocal dilutions). Non-responder rate was defined by undetectable neutralization titers for a specific variant at an initial serum dilution of 1:60 and are indicated.

(C) Ratio of mVOC ID₅₀ over the indicated WH1 ID₅₀ calculated for the groups with plasma samples at 1 month (shown in 1B) after the second vaccine dose. Horizontal bars indicate ratio geometric means for each group and error bars indicate 95% confidence intervals. Bottom numbers indicate the geometric mean of the ratio for each group. Significant p values are indicated for comparisons between uninfected and previously infected groups (Mann-Whitney test, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001). Non-responder samples are indicated by an open circle. See also Figure S2.