TY - JOUR
T1 - Vaccine-associated enhanced respiratory pathology in COVID-19 hamsters after TH2-biased immunization
AU - Ebenig, Aileen
AU - Muraleedharan, Samada
AU - Kazmierski, Julia
AU - Todt, Daniel
AU - Auste, Arne
AU - Anzaghe, Martina
AU - Gömer, André
AU - Postmus, Dylan
AU - Gogesch, Patricia
AU - Niles, Marc
AU - Plesker, Roland
AU - Miskey, Csaba
AU - Gellhorn Serra, Michelle
AU - Breithaupt, Angele
AU - Hörner, Cindy
AU - Kruip, Carina
AU - Ehmann, Rosina
AU - Ivics, Zoltan
AU - Waibler, Zoe
AU - Pfaender, Stephanie
AU - Wyler, Emanuel
AU - Landthaler, Markus
AU - Kupke, Alexandra
AU - Nouailles, Geraldine
AU - Goffinet, Christine
AU - Brown, Richard J.P.
AU - Mühlebach, Michael D.
PY - 2022/8/16
Y1 - 2022/8/16
N2 - 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 (TH1)-biased measles vaccine-derived candidate and a TH2-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, TH2-driving interleukin (IL)-19, or TH2 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 TH2 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 TH2-biased vaccination.
AB - 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 (TH1)-biased measles vaccine-derived candidate and a TH2-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, TH2-driving interleukin (IL)-19, or TH2 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 TH2 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 TH2-biased vaccination.
KW - ADE
KW - antibody-dependent enhancement
KW - COVID-19 vaccines
KW - CP: Immunology
KW - CP: Microbiology
KW - dexamethasone treatment
KW - mechanism of immunopathogenesis
KW - protein vaccines
KW - TH2 immune responses
KW - vaccine safety
KW - vaccine-associated enhanced respiratory disease
KW - VAERD
U2 - 10.1016/j.celrep.2022.111214
DO - 10.1016/j.celrep.2022.111214
M3 - Article
SN - 2639-1856
VL - 40
JO - Cell Reports
JF - Cell Reports
IS - 7
M1 - 111214
ER -
