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

2023-01-01

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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 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.