American mink as an animal model to study SARS-CoV-2 and vaccine response

Aaltonen, K.; Virtanen, J.; Kegler, K.; Venkat, V.; Kareinen, L.; Korhonen, E. M.; Niamsap, T.; Malmgren, R.; Korpela, J.; Naves, R. A.; Iso-Oja, M.; Svenns, S.; Haggvik, T.; Ojala, E.; Vapalahti, O.; Peura, J.; Sukura, A.; Ritvos, O.; Pasternack, A.; Nordgren, H.; Kant, R.; Sironen, T.

doi:10.1101/2025.06.10.658224

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bioRxiv · 10.1101/2025.06.10.658224

American mink as an animal model to study SARS-CoV-2 and vaccine response

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Abstract

Selecting a suitable animal model is crucial in understanding infectious diseases and developing vaccines. Here, we developed a receptor-binding domain -based SARS-CoV-2 vaccine with mouse Fc an immunopotentiator in a mink model. Four different variations of the vaccine were tested in groups of 30-31 American mink and followed for IgG and neutralizing antibodies (nAb) up to 27 weeks. Subcutaneous version induced a strong IgG and nAb response within two weeks and was still detectable at 27 weeks. Intranasal version also caused a detectable, although weaker, immune response. A simultaneously given subcutaneous vaccine against virus enteritis, botulism and hemorrhagic pneumonia potentially caused a lower SARS-CoV-2 antibody response, highlighting the need for further studies on co-effects of vaccines. In virus challenge with Alpha variant (B.1.1.7), vaccinated mink had a stronger antibody response than unvaccinated mink. Despite not preventing the infection, vaccinated mink had milder clinical signs and less virus in saliva. Another challenge of unvaccinated mink with Omicron variant showed similar results to alpha (BA.1) variant. Virus RNA was detected in the brain of unvaccinated mink but not vaccinated mink by in situ hybridization, indicating a suitability of mink to study neurological effects of SARS-CoV-2 and potentially long COVID as well. Author summaryFinding a good animal model is very important in studying infectious diseases and their treatment. The recent SARS-CoV2 pandemic highlighted this dilemma. We have developed an animal model based on mink due to their close match to humans in the symptomology of this disease. Such model will enable the study of relative susceptibility, transmission, tissue tropism, complex pathogenesis and long COVID, as well as prophylaxis and vaccines. This model will also help reduce the use of primates in this research. We have further developed a new vaccine for SARS-CoV2 based on the receptor binding domain of the S-protein with an inbuilt immune-enhancer. This vaccine underwent extensive testing in mink to determine response, long term protection, and safety. The vaccine was found to provide excellent titers of neutralizing antibodies with wide range in target variants. It also reduced the severity and duration of visible symptoms in the animals significantly. We propose this vaccine candidate for further study and future commercialization.

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Aaltonen, K., Virtanen, J., Kegler, K., Venkat, V., Kareinen, L., Korhonen, E. M., Niamsap, T., Malmgren, R., Korpela, J., Naves, R. A., Iso-Oja, M., Svenns, S., Haggvik, T., Ojala, E., Vapalahti, O., Peura, J., Sukura, A., Ritvos, O., Pasternack, A., Nordgren, H., Kant, R., Sironen, T.. 2025-06-11. American mink as an animal model to study SARS-CoV-2 and vaccine response. https://doi.org/10.1101/2025.06.10.658224

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