1. MVA-based vaccine candidates encoding the native or prefusion-stabilized SARS-CoV-2 spike reveal differential immunogenicity in humans.
- Author
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Mayer, Leonie, Weskamm, Leonie M., Fathi, Anahita, Kono, Maya, Heidepriem, Jasmin, Krähling, Verena, Mellinghoff, Sibylle C., Ly, My Linh, Friedrich, Monika, Hardtke, Svenja, Borregaard, Saskia, Hesterkamp, Thomas, Loeffler, Felix F., Volz, Asisa, Sutter, Gerd, Becker, Stephan, Dahlke, Christine, and Addo, Marylyn M.
- Subjects
IMMUNE response ,VACCINE immunogenicity ,SARS-CoV-2 ,COVID-19 pandemic ,CELL fusion ,VACCINIA ,GENETIC vectors ,AVIAN influenza - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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