Journal article
Nirmatrelvir treatment of SARS-CoV-2-infected mice blunts antiviral adaptive immune responses
EMBO molecular medicine, Vol.15(5), e17580
03/22/2023
DOI: 10.15252/emmm.202317580
PMCID: PMC10165354
PMID: 36946379
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.
Details
- Title: Subtitle
- Nirmatrelvir treatment of SARS-CoV-2-infected mice blunts antiviral adaptive immune responses
- Creators
- Valeria Fumagalli - Vita-Salute San Raffaele UniversityPietro Di Lucia - Vita-Salute San Raffaele UniversityMicol Ravà - Vita-Salute San Raffaele UniversityDavide Marotta - Vita-Salute San Raffaele UniversityElisa Bono - Division of Immunology, Transplantation, and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, ItalyStefano Grassi - Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, ItalyLorena Donnici - INGM - Istituto Nazionale di Genetica Molecolare "Romeo ed Erica Invernizzi", Milan, ItalyRolando Cannalire - University of Naples Federico IIIrina Stefanelli - University of Naples Federico IIAnastasia Ferraro - University of Naples Federico IIFrancesca Esposito - VITA (Germany)Elena Pariani - University of MilanDonato Inverso - Vita-Salute San Raffaele UniversityCamilla Montesano - Sapienza University of RomeSerena Delbue - University of MilanStanley Perlman - Department of Pediatrics, University of Iowa, Iowa City, IA, USAEnzo Tramontano - VITA (Germany)Raffaele De Francesco - University of MilanVincenzo Summa - University of Naples Federico IILuca G Guidotti - Vita-Salute San Raffaele UniversityMatteo Iannacone - Imaging Center
- Resource Type
- Journal article
- Publication Details
- EMBO molecular medicine, Vol.15(5), e17580
- DOI
- 10.15252/emmm.202317580
- PMID
- 36946379
- PMCID
- PMC10165354
- NLM abbreviation
- EMBO Mol Med
- ISSN
- 1757-4676
- eISSN
- 1757-4684
- Grant note
- 957502 / EC | ERC | HORIZON EUROPE European Research Council (ERC) 725038 / EC | ERC | HORIZON EUROPE European Research Council (ERC) 22737 / Fondazione AIRC per la ricerca sul cancro ETS (AIRC) 19891 / Fondazione AIRC per la ricerca sul cancro ETS (AIRC) PE00000007,INF-ACT / Ministero dell'Università e della Ricerca (MUR) RF-2018-12365801 / Ministero della Salute (Italy Ministry of Health)
- Language
- English
- Date published
- 03/22/2023
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
- Record Identifier
- 9984380371902771
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