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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Summary: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.
ISSN:2059-0105