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Vaccine-associated enhanced respiratory pathology in COVID-19 hamsters after T(H)2-biased immunization

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Item Type:Article
Title:Vaccine-associated enhanced respiratory pathology in COVID-19 hamsters after T(H)2-biased immunization
Creators Name:Ebenig, A. and Muraleedharan, S. and Kazmierski, J. and Todt, D. and Auste, A. and Anzaghe, M. and Gömer, A. and Postmus, D. and Gogesch, P. and Niles, M. and Plesker, R. and Miskey, C. and Gellhorn Serra, M. and Breithaupt, A. and Hörner, C. and Kruip, C. and Ehmann, R. and Ivics, Z. and Waibler, Z. and Pfaender, S. and Wyler, E. and Landthaler, M. and Kupke, A. and Nouailles, G. and Goffinet, C. and Brown, R.J.P and Mühlebach, M.D.
Abstract: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.
Keywords:COVID-19 Vaccines, Vaccine-Associated Enhanced Respiratory Disease, VAERD, Mechanism Of Immunopathogenesis, Antibody-Dependent Enhancement, ADE, TH2 Immune Responses, Vaccine Safety, Dexamethasone Treatment, Protein Vaccines, Animals, Hamsters, Mice
Source:Cell Reports
Publisher:Cell Press / Elsevier
Page Range:111214
Date:16 August 2022
Official Publication:https://doi.org/10.1016/j.celrep.2022.111214
PubMed:View item in PubMed

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