| Autor: |
Aileen Ebenig, Samada Muraleedharan, Julia Kazmierski, Daniel Todt, Arne Auste, Martina Anzaghe, André Gömer, Dylan Postmus, Patricia Gogesch, Marc Niles, Roland Plesker, Csaba Miskey, Michelle Gellhorn Serra, Angele Breithaupt, Cindy Hörner, Carina Kruip, Rosina Ehmann, Zoltan Ivics, Zoe Waibler, Stephanie Pfaender, Emanuel Wyler, Markus Landthaler, Alexandra Kupke, Geraldine Nouailles, Christine Goffinet, Richard J.P. Brown, Michael D. Mühlebach |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Popis: |
Vaccine-associated enhanced respiratory disease (VAERD) is a severe complication for some respiratory infections. To investigate the potential for VAERD induction in coronavirus disease 2019 (COVID-19), we evaluate two vaccine leads utilizing a severe hamster infection model: a T helper type 1 (T(H)1)-biased measles vaccine-derived candidate and a T(H)2-biased alum-adjuvanted, non-stabilized spike protein. The measles virus (MeV)-derived vaccine protects the animals, but the protein lead induces VAERD, which can be alleviated by dexamethasone treatment. Bulk transcriptomic analysis reveals that our protein vaccine prepares enhanced host gene dysregulation in the lung, exclusively up-regulating mRNAs encoding the eosinophil attractant CCL-11, T(H)2-driving interleukin (IL)-19, or T(H)2 cytokines IL-4, IL-5, and IL-13. Single-cell RNA sequencing (scRNA-seq) identifies lung macrophages or lymphoid cells as sources, respectively. Our findings imply that VAERD is caused by the concerted action of hyperstimulated macrophages and T(H)2 cytokine-secreting lymphoid cells and potentially links VAERD to antibody-dependent enhancement (ADE). In summary, we identify the cytokine drivers and cellular contributors that mediate VAERD after T(H)2-biased vaccination. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
