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Nirmatrelvir treatment blunts the development of antiviral adaptive immune responses in SARS-CoV-2 infected mice
Valeria Fumagalli; Pietro Di Lucia; Micol Rava; Davide Marotta; Elisa Bono; Stefano Grassi; Lorena Donnici; Rolando Cannalire; Irina Stefanelli; Anastasia Ferraro; Francesca Esposito; Elena Pariani; Donato Inverso; Camilla Montesano; Serena Delbue; Enzo Tramontano; Raffaele De Francesco; Vincenzo Summa; Luca Guidotti; Matteo Iannacone.
Affiliation
  • Valeria Fumagalli; Vita Salute San Raffaele University, 20132 Milan, Italy
  • Pietro Di Lucia; Division of Immunology, Transplantation, and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
  • Micol Rava; Division of Immunology, Transplantation, and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
  • Davide Marotta; Vita-Salute San Raffaele University, 20132 Milan, Italy
  • Elisa Bono; Division of Immunology, Transplantation, and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
  • Stefano Grassi; Pathology Unit, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
  • Lorena Donnici; INGM Istituto Nazionale di Genetica Molecolare Romeo ed Erica Invernizzi, 20122 Milan, Italy
  • Rolando Cannalire; Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy
  • Irina Stefanelli; Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy
  • Anastasia Ferraro; Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy
  • Francesca Esposito; Dipartimento di Scienze della Vita e dell Ambiente, Cittadella Universitaria di Monserrato, 09042 Monserrato, Cagliari, Italy
  • Elena Pariani; Department of Biomedical Sciences for Health, University of Milan, 20133 Milan, Italy
  • Donato Inverso; Vita Salute San Raffaele University, 20132 Milan, Italy
  • Camilla Montesano; Department of Chemistry, La Sapienza University, 00185 Rome, Italy
  • Serena Delbue; Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy
  • Enzo Tramontano; Dipartimento di Scienze della Vita e dell Ambiente, Cittadella Universitaria di Monserrato, 09042 Monserrato, Cagliari, Italy
  • Raffaele De Francesco; INGM Istituto Nazionale di Genetica Molecolare Romeo ed Erica Invernizzi, 20122 Milan, Italy
  • Vincenzo Summa; Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy
  • Luca Guidotti; Vita Salute San Raffaele University, 20132 Milan, Italy
  • Matteo Iannacone; Division of Immunology, Transplantation, and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
Preprint in English | bioRxiv | ID: ppbiorxiv-517465
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.
License
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Full text: Available Collection: Preprints Database: bioRxiv Type of study: Prognostic study Language: English Year: 2022 Document type: Preprint
Full text: Available Collection: Preprints Database: bioRxiv Type of study: Prognostic study Language: English Year: 2022 Document type: Preprint
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