biostudies-literatureMarcos-Villar LSpanish State Research AgencyInstituto de Salud Carlos IIIFondo Europeo para el Desarrollo Regional (FEDER) the CERCA Programme/Generalitat de Catalunya2387906https://www.ebi.ac.uk/biostudies/studies/S-EPMC11313003biostudies-literatureUnknown13(1)Despite the high efficiency of current SARS-CoV-2 mRNA vaccines in reducing COVID-19 morbidity and mortality, waning immunity and the emergence of resistant variants underscore the need for novel vaccination strategies. This study explores a heterologous mRNA/Modified Vaccinia virus Ankara (MVA) prime/boost regimen employing a trimeric form of the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein compared to a homologous MVA/MVA regimen. In C57BL/6 mice, the RBD was delivered during priming via an mRNA vector encapsulated in nanoemulsions (NE) or lipid nanoparticles (LNP), followed by a booster with a replication-deficient MVA-based recombinant virus (MVA-RBD). This heterologous mRNA/MVA regimen elicited strong anti-RBD binding and neutralizing antibodies (BAbs and NAbs) agEmerging microbes & infectionsHeterologous mRNA/MVA delivering trimeric-RBD as effective vaccination regimen against SARS-CoV-2: COVARNA Consortium.PMC11313003SGR 653ICI20/00067COV20/00214SGR 615PI18/00699PID2020-117425RB-C22FIS PI22/00814Sorzano COSEsteban IPerdiguero BSistere-Oro MCuesta BEsteban MCasasnovas JMSanchez-Cordon PJZamora CAstorgano DLopez-Bigas NAlonso MJThielemans KSin LGomez CEAlvarez EPlana MAnthiya SFranceschini LBorrajo MLLopez-Bravo MMarcos-Villar LGelpi JLGarcia FMeyerhans ALou GGarcia-Arriaza JfalseHeterologous mRNA/MVA delivering trimeric-RBD as effective vaccination regimen against SARS-CoV-2: COVARNA Consortium.Despite the high efficiency of current SARS-CoV-2 mRNA vaccines in reducing COVID-19 morbidity and mortality, waning immunity and the emergence of resistant variants underscore the need for novel vaccination strategies. This study explores a heterologous mRNA/Modified Vaccinia virus Ankara (MVA) prime/boost regimen employing a trimeric form of the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein compared to a homologous MVA/MVA regimen. In C57BL/6 mice, the RBD was delivered during priming via an mRNA vector encapsulated in nanoemulsions (NE) or lipid nanoparticles (LNP), followed by a booster with a replication-deficient MVA-based recombinant virus (MVA-RBD). This heterologous mRNA/MVA regimen elicited strong anti-RBD binding and neutralizing antibodies (BAbs and NAbs) ag2024-01-01T00:00:00Z2024 Dec2026-04-07T16:05:52.318Z2024-11-05T16:10:50.075ZS-EPMC113130033908755510.1080/22221751.2024.2387906