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- Title
MVA-based vaccine candidates encoding the native or prefusion-stabilized SARS-CoV-2 spike reveal differential immunogenicity in humans.
- Authors
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; Addo, Marylyn M.
- 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.
- Subjects
CHAD; ANKARA (Turkey); IMMUNE response; VACCINE immunogenicity; SARS-CoV-2; COVID-19 pandemic; CELL fusion; VACCINIA; GENETIC vectors; AVIAN influenza
- Publication
NPJ Vaccines, 2024, Vol 9, Issue 1, p1
- ISSN
2059-0105
- Publication type
Article
- DOI
10.1038/s41541-023-00801-z