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学術論文

MVA-based vaccine candidates encoding the native or prefusion-stabilized SARS-CoV-2 spike reveal differential immunogenicity in humans

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Heidepriem,  Jasmin
Felix Löffler, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Löffler,  Felix F.
Felix Löffler, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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引用

Mayer, L., Weskamm, L. M., Fathi, A., Kono, M., Heidepriem, J., Krähling, V., Mellinghoff, S. C., Ly, M. L., Friedrich, M., Hardtke, S., Borregaard, S., Hesterkamp, T., Löffler, F. F., Volz, A., Sutter, G., Becker, S., Dahlke, C., & Addo, M. M. (2024). MVA-based vaccine candidates encoding the native or prefusion-stabilized SARS-CoV-2 spike reveal differential immunogenicity in humans. npj Vaccines, 9(1):. doi:10.1038/s41541-023-00801-z.


引用: https://hdl.handle.net/21.11116/0000-000E-538C-7
要旨
In 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.