Mayer, LeonieLeonieMayerWeskamm, Leonie MarieLeonie MarieWeskammFathi, AnahitaAnahitaFathiKono, MayaMayaKonoHeidepriem, JasminJasminHeidepriemKrähling, VerenaVerenaKrählingMellinghoff, Sibylle C.Sibylle C.MellinghoffLy, My LinhMy LinhLyFriedrich, MonikaMonikaFriedrichHardtke, SvenjaSvenjaHardtkeBorregaard, SaskiaSaskiaBorregaardHesterkamp, ThomasThomasHesterkampLoeffler, Felix F.Felix F.LoefflerVolz, AsisaAsisaVolzSutter, GerdGerdSutterBecker, StephanStephanBeckerDahlke, ChristineChristineDahlkeAddo, MarylynMarylynAddo2025-12-042025-12-042024-12-01Npj Vaccines 9 (1): 20 (2024)https://hdl.handle.net/11420/59414In response to the COVID-19 pandemic, multiple vaccines were developed using platforms such as viral vectors and mRNA technology. Here, we report humoral and cellular immunogenicity data from human phase 1 clinical trials investigating two recombinant Modified Vaccinia virus Ankara vaccine candidates, MVA-SARS-2-S and MVA-SARS-2-ST, encoding the native and the prefusion-stabilized SARS-CoV-2 spike protein, respectively. MVA-SARS-2-ST was more immunogenic than MVA-SARS-2-S, but both were less immunogenic compared to licensed mRNA- and ChAd-based vaccines in SARS-CoV-2 naïve individuals. In heterologous vaccination, previous MVA-SARS-2-S vaccination enhanced T cell functionality and MVA-SARS-2-ST boosted the frequency of T cells and S1-specific IgG levels when used as a third vaccination. While the vaccine candidate containing the prefusion-stabilized spike elicited predominantly S1-specific responses, immunity to the candidate with the native spike was skewed towards S2-specific responses. These data demonstrate how the spike antigen conformation, using the same viral vector, directly affects vaccine immunogenicity in humans.en#PLACEHOLDER_PARENT_METADATA_VALUE#20241Technology::600: TechnologyJournal Article10.1038/s41541-023-00801-zJournal Article