摘要Periodically updating coronavirus disease 19(COVID-19)vaccines that offer broad-spectrum protection is needed given the strong immune evasion by the circulating omicron sublineages.The effectiveness of prototype and BA.4/5-contain-ing bivalent mRNA vaccines is reduced when XBB subvariants predominate.We initiated an observer-blinded,three-arms study in 376 patients in Chinese individuals aged from 18 to 55 years old who had previously received three doses COVID-19 vaccine.Immunogenicity in terms of neutralizing antibodies elicited by a 30-pg dose of XBB.1.5-containing bivalent vaccine(RQ3027),a 30-pg dose of BA.2/BA.5-Alpha/Beta bivalent vaccine(RQ3025)and their precedent 30-pg Alpha/Beta(combined mutations)monovalent mRNA vaccine(RQ3013)and safety are primary and secondary end-points,respectively.We recorded prescribed COVID-19 cases to explore the preliminary efficacy of three vaccines.RQ3027 and RQ3025 boosters elicited superior neutralizing antibodies(NAbs)against XBB.1.5,XBB.1.16,XBB.1.9.1,and JN.1 compared to RQ3013 at day 14 in participants without SARS-CoV-2 infection.All study vaccines were well-tolerated without serious adverse reactions identified.The incidence rates per 1000 person-years of COVID-19 cases during the 2nd-19th week after randomization were lowest in RQ3027.Overall,our data show that XBB.1.5-containing bivalent booster generated superior immunogenicity and better protection against newer severe acute respiratory syn-drome coronavirus 2(SARS-CoV-2)variants compared to BA.2/BA.5-containing bivalent and Alpha/Beta monovalent with no new safety concerns.