Statistical analysis
The statistical analyses were done separately for two different cohorts (2C and 3C cohorts). Safety profiles were assessed in the safety set (SS) of participants who received one booster dose. Immunological endpoints were assessed in the per-protocol set (PPS), which included all participants who completed one booster dose and had available neutralizing antibody results according to the protocol, as well as all back-up serum samples with available neutralizing antibody results. According to the timepoints postvaccination, PPS was divided into PPS1 (Day 7), PPS2 (Day 14) and PPS3 (Day 28). The demographics of participants in the full analysis set (FAS) were summarized by cohorts and vaccination groups. Pearson chi-squared test or Fisher’s exact test were applied to analyze categorical variables for group comparison, and t-tests or analysis of variance (ANOVA) were used for continuous variables.For the primary objectives, superiority is considered to be fulfilled when the lower boundary of 95% confidence intervals (CIs) for the GMT ratio is >1, which is equivalent to the GMT difference after logObserved GMTs and corresponding 95%CIs were calculated based on a standard normal distribution of log-transformed neutralizing antibody titers, of which titers lower than the lower limit of quantitation (LLOQ, 1:4) were presented as half of LLOQ. Analysis of covariance (ANCOVA) was used to compare the difference between groups, which used log-transformed antibody titers after vaccination as the dependent variable, study vaccines and age (18-59 or ≥60 years) as the fixed effects, and log-transformed antibody titers before vaccination as the covariate. GMTs and 95% CIs were then estimated by the geometric least-square mean from the ANCOVA model, and the differences in antibody responses between groups were estimated by the ratio of geometric least-square mean and 95% CIs. Seroconversion refers to GMT changes from <LLOQ to ≥4-fold LLOQ (1:16) after vaccination, or at least 4-fold increases after vaccination if baseline GMT is ≥LLOQ. The corresponding 95%CIs of seroconversions were calculated according to Clopper-Pearson analysis, and seroconversion rate differences and 95%CIs between groups were estimated by the age stratified (18-59 or ≥60 years) Cochran-Mantel-Haenszel test.Subgroup analyses were performed by age (18-59 and ≥60 years) for neutralizing antibodies. Exploratory analyses were applied to evaluate the antibodies response at 7 and 14 days after vaccination in the immunogenicity subgroup participants. Hypothesis testing was two-sided, and p values of less than 0.05 were considered to be significant. All analyses were conducted with SAS (Version 9.4, SAS Institute Inc., Cary, USA).