Hamsters immunized with formalin-inactivated SARS-CoV-2 develop accelerated lung histopathological lesions and Th2-biased response following infection

Abstract One of the concerns regarding vaccine safety during the COVID-19 pandemic was the potential manifestation of vaccine-associated enhancement of disease (VAED) upon SARS-CoV-2 infection. To investigate the suitability of the Syrian hamster model to test for VAED, we immunized animals with an...

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Main Authors: Rineke de Jong, Sandra Vreman, Katrin E. Wiese, Nora M. Gerhards, Kevin R. Bewley, Yper Hall, Francisco Javier Salguero, Miles Carroll, Rik L. de Swart, Jose L. Gonzales, Nadia Oreshkova
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:npj Vaccines
Online Access:https://doi.org/10.1038/s41541-025-01160-7
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author Rineke de Jong
Sandra Vreman
Katrin E. Wiese
Nora M. Gerhards
Kevin R. Bewley
Yper Hall
Francisco Javier Salguero
Miles Carroll
Rik L. de Swart
Jose L. Gonzales
Nadia Oreshkova
author_facet Rineke de Jong
Sandra Vreman
Katrin E. Wiese
Nora M. Gerhards
Kevin R. Bewley
Yper Hall
Francisco Javier Salguero
Miles Carroll
Rik L. de Swart
Jose L. Gonzales
Nadia Oreshkova
author_sort Rineke de Jong
collection DOAJ
description Abstract One of the concerns regarding vaccine safety during the COVID-19 pandemic was the potential manifestation of vaccine-associated enhancement of disease (VAED) upon SARS-CoV-2 infection. To investigate the suitability of the Syrian hamster model to test for VAED, we immunized animals with an experimental formaldehyde-inactivated, alum-adjuvanted SARS-CoV-2 vaccine preparation. In two independent experiments, challenge infection did not result in an enhancement of the clinical disease in vaccinated animals compared with mock-vaccinated animals. However, at early timepoints (2–5 days) post-challenge, lung histopathology progressed faster and was more prominent in vaccinated hamsters and lung tissue showed elevated mRNA levels of IL-4 and IL-13. At later time points, cytokine responses and lung pathology were comparable between vaccinated and mock-vaccinated hamsters, underscoring the transient nature of the pathological aggravation. With this work we show that the Syrian hamster model can be used to assess possible vaccine safety considerations in a preclinical setting.
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spelling doaj-art-0edf54eaa75449cb87cec45fb37c4b682025-08-20T03:03:23ZengNature Portfolionpj Vaccines2059-01052025-07-0110111910.1038/s41541-025-01160-7Hamsters immunized with formalin-inactivated SARS-CoV-2 develop accelerated lung histopathological lesions and Th2-biased response following infectionRineke de Jong0Sandra Vreman1Katrin E. Wiese2Nora M. Gerhards3Kevin R. Bewley4Yper Hall5Francisco Javier Salguero6Miles Carroll7Rik L. de Swart8Jose L. Gonzales9Nadia Oreshkova10Wageningen Bioveterinary Research, Wageningen University and ResearchWageningen Bioveterinary Research, Wageningen University and ResearchWageningen Bioveterinary Research, Wageningen University and ResearchWageningen Bioveterinary Research, Wageningen University and ResearchUnited Kingdom Health Security Agency (UKHSA), Porton DownUnited Kingdom Health Security Agency (UKHSA), Porton DownUnited Kingdom Health Security Agency (UKHSA), Porton DownCentre for Human Genetics and the Pandemic Sciences Institute, Nuffield Department of Medicine, University of OxfordWageningen Bioveterinary Research, Wageningen University and ResearchWageningen Bioveterinary Research, Wageningen University and ResearchWageningen Bioveterinary Research, Wageningen University and ResearchAbstract One of the concerns regarding vaccine safety during the COVID-19 pandemic was the potential manifestation of vaccine-associated enhancement of disease (VAED) upon SARS-CoV-2 infection. To investigate the suitability of the Syrian hamster model to test for VAED, we immunized animals with an experimental formaldehyde-inactivated, alum-adjuvanted SARS-CoV-2 vaccine preparation. In two independent experiments, challenge infection did not result in an enhancement of the clinical disease in vaccinated animals compared with mock-vaccinated animals. However, at early timepoints (2–5 days) post-challenge, lung histopathology progressed faster and was more prominent in vaccinated hamsters and lung tissue showed elevated mRNA levels of IL-4 and IL-13. At later time points, cytokine responses and lung pathology were comparable between vaccinated and mock-vaccinated hamsters, underscoring the transient nature of the pathological aggravation. With this work we show that the Syrian hamster model can be used to assess possible vaccine safety considerations in a preclinical setting.https://doi.org/10.1038/s41541-025-01160-7
spellingShingle Rineke de Jong
Sandra Vreman
Katrin E. Wiese
Nora M. Gerhards
Kevin R. Bewley
Yper Hall
Francisco Javier Salguero
Miles Carroll
Rik L. de Swart
Jose L. Gonzales
Nadia Oreshkova
Hamsters immunized with formalin-inactivated SARS-CoV-2 develop accelerated lung histopathological lesions and Th2-biased response following infection
npj Vaccines
title Hamsters immunized with formalin-inactivated SARS-CoV-2 develop accelerated lung histopathological lesions and Th2-biased response following infection
title_full Hamsters immunized with formalin-inactivated SARS-CoV-2 develop accelerated lung histopathological lesions and Th2-biased response following infection
title_fullStr Hamsters immunized with formalin-inactivated SARS-CoV-2 develop accelerated lung histopathological lesions and Th2-biased response following infection
title_full_unstemmed Hamsters immunized with formalin-inactivated SARS-CoV-2 develop accelerated lung histopathological lesions and Th2-biased response following infection
title_short Hamsters immunized with formalin-inactivated SARS-CoV-2 develop accelerated lung histopathological lesions and Th2-biased response following infection
title_sort hamsters immunized with formalin inactivated sars cov 2 develop accelerated lung histopathological lesions and th2 biased response following infection
url https://doi.org/10.1038/s41541-025-01160-7
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