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, Valeria; Di Lucia, Pietro; Ravà, Micol; Marotta, Davide; Bono, Elisa; Grassi, Stefano; Donnici, Lorena; Cannalire, Rolando; Stefanelli, Irina; Ferraro, Anastasia; Esposito, Francesca; Pariani, Elena; Inverso, Donato; Montesano, Camilla; Delbue, Serena; Perlman, Stanley; Tramontano, Enzo; De Francesco, Raffaele; Summa, Vincenzo; Guidotti, Luca G; Iannacone, Matteo. - 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

Fumagalli, Valeria
Primo
;
Marotta, Davide;Inverso, Donato;Guidotti, Luca G
Penultimo
;
Iannacone, Matteo
Ultimo
2023-01-01

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.
2023
SARS-CoV-2
adaptive immunity
animal models
antiviral treatment
nirmatrelvir
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/158418
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