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Nirmatrelvir\u2014an orally available inhibitor of the 3\u2010chymotrypsin\u2010like cysteine protease\u2014has been shown to reduce the risk of progression to severe COVID\u201019. However, the impact of nirmatrelvir treatment on the development of SARS\u2010CoV\u20102\u2010specific adaptive immune responses is unknown. Here, by using mouse models of SARS\u2010CoV\u20102 infection, we show that nirmatrelvir administration blunts the development of SARS\u2010CoV\u20102\u2010specific antibody and T cell responses. Accordingly, upon secondary challenge, nirmatrelvir\u2010treated 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.<\/jats:p>","DOI":"10.15252\/emmm.202317580","type":"journal-article","created":{"date-parts":[[2023,3,22]],"date-time":"2023-03-22T06:50:40Z","timestamp":1679467840000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Nirmatrelvir treatment of SARS\u2010CoV\u20102\u2010infected mice blunts antiviral adaptive immune responses"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2583-2498","authenticated-orcid":false,"given":"Valeria","family":"Fumagalli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Di Lucia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micol","family":"Rav\u00e0","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Marotta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Bono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Grassi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9153-9102","authenticated-orcid":false,"given":"Lorena","family":"Donnici","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolando","family":"Cannalire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8861-4829","authenticated-orcid":false,"given":"Irina","family":"Stefanelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Ferraro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9725-7977","authenticated-orcid":false,"given":"Francesca","family":"Esposito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Pariani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0987-3345","authenticated-orcid":false,"given":"Donato","family":"Inverso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Montesano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Delbue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4213-2354","authenticated-orcid":false,"given":"Stanley","family":"Perlman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4849-0980","authenticated-orcid":false,"given":"Enzo","family":"Tramontano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8754-5123","authenticated-orcid":false,"given":"Raffaele","family":"De Francesco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6288-2681","authenticated-orcid":false,"given":"Vincenzo","family":"Summa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0205-2678","authenticated-orcid":false,"given":"Luca G","family":"Guidotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9370-2671","authenticated-orcid":false,"given":"Matteo","family":"Iannacone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,3,22]]},"reference":[{"key":"BFEMMM202317580_CR1","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1038\/ni1098","volume":"5","author":"VP Badovinac","year":"2004","unstructured":"Badovinac VP, Porter BB, Harty JT (2004) CD8+ T cell contraction is controlled by early inflammation. 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