Full text

Turn on search term navigation

© 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

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
Nirmatrelvir treatment of SARS-CoV-2-infected mice blunts antiviral adaptive immune responses
Author
Fumagalli, Valeria 1   VIAFID ORCID Logo  ; Pietro Di Lucia 1 ; Ravà, Micol 1 ; Marotta, Davide 1 ; Bono, Elisa 2 ; Grassi, Stefano 3 ; Donnici, Lorena 4   VIAFID ORCID Logo  ; Cannalire, Rolando 5 ; Stefanelli, Irina 5   VIAFID ORCID Logo  ; Ferraro, Anastasia 5 ; Esposito, Francesca 6   VIAFID ORCID Logo  ; Pariani, Elena 7 ; Donato Inverso 1   VIAFID ORCID Logo  ; Montesano, Camilla 8 ; Delbue, Serena 9 ; Perlman, Stanley 10   VIAFID ORCID Logo  ; Tramontano, Enzo 6   VIAFID ORCID Logo  ; De Francesco, Raffaele 11   VIAFID ORCID Logo  ; Summa, Vincenzo 5   VIAFID ORCID Logo  ; Guidotti, Luca G 1   VIAFID ORCID Logo  ; Iannacone, Matteo 12   VIAFID ORCID Logo 

 Division of Immunology, Transplantation, and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy 
 Division of Immunology, Transplantation, and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy 
 Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy 
 INGM - Istituto Nazionale di Genetica Molecolare “Romeo ed Erica Invernizzi”, Milan, Italy 
 Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy 
 Dipartimento di Scienze della Vita e dell'Ambiente, Cittadella Universitaria di Monserrato, Cagliari, Italy 
 Department of Biomedical Sciences for Health, University of Milan, Milan, Italy 
 Department of Chemistry, La Sapienza University, Rome, Italy 
 Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy 
10  Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, USA; Department of Pediatrics, University of Iowa, Iowa City, IA, USA 
11  INGM - Istituto Nazionale di Genetica Molecolare “Romeo ed Erica Invernizzi”, Milan, Italy; Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy 
12  Division of Immunology, Transplantation, and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy; Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan, Italy 
Section
Reports
Publication year
2023
Publication date
May 2023
Publisher
EMBO Press
ISSN
17574676
e-ISSN
17574684
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2810788041
Copyright
© 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.