biostudies-literatureBranche ARBLRD VANIAID NIH HHSU.S. Department of Health & Human Services | NIH | National Cancer InstituteNCI NIH HHSCLC NIH HHS2334-2346https://www.ebi.ac.uk/biostudies/studies/S-EPMC10504073biostudies-literatureUnknown29(9)Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label, randomized clinical trial with sequentially enrolled stages at 22 US sites, we assessed safety and immunogenicity of a second boost with monovalent or bivalent variant vaccines from mRNA and protein-based platforms targeting wild-type, Beta, Delta and Omicron BA.1 spike antigens. The primary outcome was pseudovirus neutralization titers at 50% inhibitory dilution (ID₅₀ titers) with 95% confidence intervals against different SARS-CoV-2 strains. The secondary outcome assessed safety by solicited local and systemic adverse events (AEs), unsolicited AEs, serious AEs and AEs of special interest. Boosting with prototypNature medicineComparison of bivalent and monovalent SARS-CoV-2 variant vaccines: the phase 2 randomized open-label COVAIL trial.PMC10504073UM1 AI14845075N93021C0001475N93019C00050UM1 AI148574UM1 AI14868475N93021C00012UM1 AI148576C000000875N93021D0002175N91019D00024I01 BX000207Contract No. 75N91019D00024 Task Order No. 75N91022F00007Desrosiers AHoang BPost DJLinton JEEngelson CBaughman HArega JNayak SUSiegel MNovak RMWinokur PLMaxwell CLadner BGTong AWalsh EMahgoub SMWalsh SRBabu TMBaden LRChan AKrause TSmith DJCarste BGriffith CJSmith MJPresti RMRoberts PCMulligan MJEl Sahly HMMcDonald WLAckerley CGRooks RGoepfert PAAtmar RLLee MSteinmetz KNeuzil KMEaton AWalter EBMartin TCSMeier JUnterberger KEWalsh EEBeigel JHLewis TCPosavad CMCOVAIL Study GroupLosada CTureli SKingsley PHerrick JByrnes KDiemert DJDeGrace MMBacker MOikonomopoulou ZKottkamp ACMakowski MPeasley MHoopengardner LBRouphael NGFusco DNHendrickx SWhitaker JAWald AJackson LADrouin ACMoody MAMcNeil LElsafy MStapleton JYoung SPPeters ERupp RKoo HSherman ACDavis TSchmader KEMarrazzo JBrown EGraciaa DSFrey SEMcQuarrie LStephens DSFalsey ARMeagher MATelu KParker TPikaart-Tautges RHill HCarter NAbebe KGraham IHealy CMAbate GSamaha HBethony JMLittle SJHoft DFLyke KEEngel TMSoma VO'Halloran JALuetkemeyer AFMakhene MDunstan MLennox JNetzl AWilks SHRostad CAImmergluck LCNoor AGale MKamidani SAnderson EJBurkey AEMu JKeitel WAMontefiori DCJohnson EPorterfield LHauge KAli FGiebeig LAMalkin ENolan LLau RCrandon SBranche ARWendrow ANumbi FKThompson RMGettinger NLAlbert JHarris CFarley MMLopez AMDan CurtinShami SSindall EMcElrath JfalseComparison of bivalent and monovalent SARS-CoV-2 variant vaccines: the phase 2 randomized open-label COVAIL trial.Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label, randomized clinical trial with sequentially enrolled stages at 22 US sites, we assessed safety and immunogenicity of a second boost with monovalent or bivalent variant vaccines from mRNA and protein-based platforms targeting wild-type, Beta, Delta and Omicron BA.1 spike antigens. The primary outcome was pseudovirus neutralization titers at 50% inhibitory dilution (ID₅₀ titers) with 95% confidence intervals against different SARS-CoV-2 strains. The secondary outcome assessed safety by solicited local and systemic adverse events (AEs), unsolicited AEs, serious AEs and AEs of special interest. Boosting with prototyp2023-01-01T00:00:00Z2023 Sep2026-05-28T09:35:26.3Z2025-04-04T09:34:42.413ZS-EPMC105040733764086010.1038/s41591-023-02503-4