Nirmatrelvir treatment blunts the development of antiviral adaptive immune responses in SARS-CoV-2 infected mice

Fumagalli, V.; Di Lucia, P.; Rava, M.; Marotta, D.; Bono, E.; Grassi, S.; Donnici, L.; Cannalire, R.; Stefanelli, I.; Ferraro, A.; Esposito, F.; Pariani, E.; Inverso, D.; Montesano, C.; Delbue, S.; Tramontano, E.; De Francesco, R.; Summa, V.; Guidotti, L.; Iannacone, M.

doi:10.1101/2022.11.22.517465

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bioRxiv · 10.1101/2022.11.22.517465

Nirmatrelvir treatment blunts the development of antiviral adaptive immune responses in SARS-CoV-2 infected mice

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Abstract

Alongside vaccines, antiviral drugs are becoming an integral part of our response to the SARS-CoV-2 pandemic. Nirmatrelvir - an orally available inhibitor of the 3-chymotrypsin-like cysteine protease - has been shown to reduce the risk of progression to severe COVID-19. However, the impact of nirmatrelvir treatment on the development of SARS-CoV-2-specific adaptive immune responses is unknown. Here, by using a mouse model of SARS-CoV-2 infection, we show that nirmatrelvir administration early after infection blunts the development of SARS-CoV-2-specific antibody and T cell responses. Accordingly, upon secondary challenge, nirmatrelvir-treated mice recruited significantly fewer memory T and B cells to the infected lungs and to mediastinal lymph nodes, respectively. Together, the data highlight a potential negative impact of nirmatrelvir treatment with important implications for clinical management and might help explain the virological and/or symptomatic relapse after treatment completion reported in some individuals.

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Fumagalli, V., Di Lucia, P., Rava, M., Marotta, D., Bono, E., Grassi, S., Donnici, L., Cannalire, R., Stefanelli, I., Ferraro, A., Esposito, F., Pariani, E., Inverso, D., Montesano, C., Delbue, S., Tramontano, E., De Francesco, R., Summa, V., Guidotti, L., Iannacone, M.. 2022-11-22. Nirmatrelvir treatment blunts the development of antiviral adaptive immune responses in SARS-CoV-2 infected mice. https://doi.org/10.1101/2022.11.22.517465

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