Introduction: The possibility of vaccine-associated enhancement of disease (VAED) is a concern for vaccine safety. Hamsters are a suitable animal model for SARS-CoV-2 vaccine studies. Therefore, we investigated the potential to induce VAED in this animal model.
Materials and methods: In two separate experiments, Golden Syrian hamsters were vaccinated with differently dosed purified formaldehyde-inactivated SARS-CoV-2 vaccines (FIV) adjuvanted with Alum. Following challenge with SARS-CoV-2 viral loads, clinical disease, lung pathology and cytokine profiles (qRT-PCR and Nanostring®) were compared between vaccinated and non-vaccinated hamsters between 2 and 13 days post infection (dpi).
Results: In both experiments, FIV vaccines barely reduced viral RNA levels and did not protect against clinical disease. In the first experiment, at 5 dpi, the pulmonary changes were characterized by more prominent perivascular cuffs, alveolar infiltrates and haemorrhages, and seemed more extensive in vaccinated animals compared with non-vaccinated animals. At 13 dpi, only minimal pulmonary changes were observed in both vaccinated and non-vaccinated animals. In the second experiment, the severity of the pulmonary changes increased faster in vaccinated hamsters, and the perivascular cuffs seemed more prominent in this group. Cytokine mRNA expression revealed more pronounced Th2 responses (e.g. IL-4 and IL-13) in the lung of vaccinated hamsters early after challenge infection, with comparable levels in vaccinated and non-vaccinated hamsters at later time points.
Conclusions: Taken together, we demonstrated that lung histopathology and Th2-cell skewing kinetics are critical parameters to reveal VAED in hamsters. Thereby, the toolbox established in this model can be used to study vaccine safety in a pre-clinical setting.