Vaccine-associated enhanced respiratory pathology in COVID-19 hamsters after TH2-biased immunization

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

doi:10.1016/j.celrep.2022.111214

Vaccine-associated enhanced respiratory pathology in COVID-19 hamsters after TH2-biased immunization

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

Paul-Ehrlich-Institut
Charité – Universitätsmedizin Berlin
Ruhr University Bochum
European Virus Bioinformatics Center
German Center for Infection Research, Giessen - Marburg - Langen Partner Site
University of Veterinary Medicine Hannover, Foundation
University of Marburg
Friedrich-Loeffler-Institute
Bundeswehr
Max Delbrück Center for Molecular Medicine in the Helmholtz Association
Humboldt University of Berlin

Research output: Contribution to journal › Article › peer-review

37 Citations (Scopus)

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 (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.

Original language	English
Article number	111214
Journal	Cell Reports
Volume	40
Issue number	7
DOIs	https://doi.org/10.1016/j.celrep.2022.111214
Publication status	Published - 16 Aug 2022
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

ADE
antibody-dependent enhancement
COVID-19 vaccines
CP: Immunology
CP: Microbiology
dexamethasone treatment
mechanism of immunopathogenesis
protein vaccines
TH2 immune responses
vaccine safety
vaccine-associated enhanced respiratory disease
VAERD

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10.1016/j.celrep.2022.111214Licence: CC BY

Cite this

Ebenig, A., Muraleedharan, S., Kazmierski, J., Todt, D., Auste, A., Anzaghe, M., Gömer, A., Postmus, D., Gogesch, P., Niles, M., Plesker, R., Miskey, C., Gellhorn Serra, M., Breithaupt, A., Hörner, C., Kruip, C., Ehmann, R., Ivics, Z., Waibler, Z., ... Mühlebach, M. D. (2022). Vaccine-associated enhanced respiratory pathology in COVID-19 hamsters after TH2-biased immunization. Cell Reports, 40(7), Article 111214. https://doi.org/10.1016/j.celrep.2022.111214

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title = "Vaccine-associated enhanced respiratory pathology in COVID-19 hamsters after TH2-biased immunization",

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 (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.",

keywords = "ADE, antibody-dependent enhancement, COVID-19 vaccines, CP: Immunology, CP: Microbiology, dexamethasone treatment, mechanism of immunopathogenesis, protein vaccines, TH2 immune responses, vaccine safety, vaccine-associated enhanced respiratory disease, VAERD",

author = "Aileen Ebenig and Samada Muraleedharan and Julia Kazmierski and Daniel Todt and Arne Auste and Martina Anzaghe and Andr{\'e} G{\"o}mer and Dylan Postmus and Patricia Gogesch and Marc Niles and Roland Plesker and Csaba Miskey and \{Gellhorn Serra\}, Michelle and Angele Breithaupt and Cindy H{\"o}rner and Carina Kruip and Rosina Ehmann and Zoltan Ivics and Zoe Waibler and Stephanie Pfaender and Emanuel Wyler and Markus Landthaler and Alexandra Kupke and Geraldine Nouailles and Christine Goffinet and Brown, \{Richard J.P.\} and M{\"u}hlebach, \{Michael D.\}",

year = "2022",

month = aug,

day = "16",

doi = "10.1016/j.celrep.2022.111214",

language = "English",

volume = "40",

journal = "Cell Reports",

issn = "2639-1856",

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Ebenig, A, Muraleedharan, S, Kazmierski, J, Todt, D, Auste, A, Anzaghe, M, Gömer, A, Postmus, D, Gogesch, P, Niles, M, Plesker, R, Miskey, C, Gellhorn Serra, M, Breithaupt, A, Hörner, C, Kruip, C, Ehmann, R, Ivics, Z, Waibler, Z, Pfaender, S, Wyler, E, Landthaler, M, Kupke, A, Nouailles, G, Goffinet, C, Brown, RJP & Mühlebach, MD 2022, 'Vaccine-associated enhanced respiratory pathology in COVID-19 hamsters after TH2-biased immunization', Cell Reports, vol. 40, no. 7, 111214. https://doi.org/10.1016/j.celrep.2022.111214

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 -

Vaccine-associated enhanced respiratory pathology in COVID-19 hamsters after TH2-biased immunization

Abstract

UN SDGs

Keywords

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