: 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 mouse models of SARS-CoV-2 infection, we show that nirmatrelvir administration 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 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.
Nirmatrelvir treatment of SARS-CoV-2-infected mice blunts antiviral adaptive immune responses / Fumagalli, V., Di Lucia, P., Ravà, 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., Perlman, S., Tramontano, E., De Francesco, R., Summa, V., Guidotti, L.G., et al.. - In: EMBO MOLECULAR MEDICINE. - ISSN 1757-4684. - 15:5(2023). [10.15252/emmm.202317580]
Nirmatrelvir treatment of SARS-CoV-2-infected mice blunts antiviral adaptive immune responses
Cannalire, Rolando;Stefanelli, Irina;Ferraro, Anastasia;Summa, Vincenzo;
2023
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 mouse models of SARS-CoV-2 infection, we show that nirmatrelvir administration 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 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
