{"doi":"10.15252/emmm.202317580","title":"Nirmatrelvir treatment of SARS‐CoV‐2‐infected mice blunts antiviral adaptive immune responses","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>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.</jats:p>","journal":"EMBO Molecular Medicine","year":2023,"id":631956,"datarank":0.9278517593176497,"base_score":3.295836866004329,"endowment":3.295836866004329,"self_citation_contribution":0.4943755299006494,"citation_network_contribution":0.4334762294170003,"self_endowment_contribution":0.4943755299006494,"citer_contribution":0.4334762294170003,"corpus_percentile":null,"corpus_rank":null,"citation_count":26,"citer_count":20,"citers_with_citation_signal":17,"citers_with_endowment":17,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":814552,"name":"Pietro Di Lucia","orcid":"0000-0002-0726-1532","position":1,"is_corresponding":false},{"id":814550,"name":"Micol Ravà","orcid":"0000-0001-7606-8368","position":2,"is_corresponding":false},{"id":814553,"name":"Davide Marotta","orcid":"0000-0003-1918-050X","position":3,"is_corresponding":false},{"id":1205490,"name":"Elisa Bono","orcid":"0000-0002-5212-3446","position":4,"is_corresponding":false},{"id":1637880,"name":"Stefano Grassi","orcid":null,"position":5,"is_corresponding":false},{"id":1205499,"name":"Lorena Donnici","orcid":"0000-0002-9153-9102","position":6,"is_corresponding":false},{"id":1637881,"name":"Rolando Cannalire","orcid":null,"position":7,"is_corresponding":false},{"id":1637882,"name":"Irina Stefanelli","orcid":"0000-0002-8861-4829","position":8,"is_corresponding":false},{"id":1637883,"name":"Anastasia Ferraro","orcid":null,"position":9,"is_corresponding":false},{"id":469357,"name":"Francesca Esposito","orcid":"0000-0001-9725-7977","position":10,"is_corresponding":false},{"id":1637884,"name":"Elena Pariani","orcid":null,"position":11,"is_corresponding":false},{"id":1199303,"name":"Donato Inverso","orcid":"0000-0003-0987-3345","position":12,"is_corresponding":false},{"id":1637885,"name":"Camilla Montesano","orcid":null,"position":13,"is_corresponding":false},{"id":1637886,"name":"Serena Delbue","orcid":null,"position":14,"is_corresponding":false},{"id":77538,"name":"Stanley Perlman","orcid":"0000-0003-4213-2354","position":15,"is_corresponding":false},{"id":469359,"name":"Enzo Tramontano","orcid":"0000-0002-4849-0980","position":16,"is_corresponding":false},{"id":592168,"name":"Raffaele De Francesco","orcid":"0000-0001-8754-5123","position":17,"is_corresponding":false},{"id":1637887,"name":"Vincenzo Summa","orcid":"0000-0002-6288-2681","position":18,"is_corresponding":false},{"id":1205500,"name":"Luca G. Guidotti","orcid":"0000-0002-0205-2678","position":19,"is_corresponding":false},{"id":52959,"name":"Matteo Iannacone","orcid":"0000-0002-9370-2671","position":20,"is_corresponding":false},{"id":814551,"name":"Valeria Fumagalli","orcid":"0000-0003-2583-2498","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Nirmatrelvir treatment of SARS‐CoV‐2‐infected mice blunts antiviral adaptive immune responses","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>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.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"36946379","pmcid":"PMC10165354","openalex_id":null,"authors":[],"funders":[{"funder_name":"EC | ERC | HORIZON EUROPE European Research Council","grant_id":"725038","title":null},{"funder_name":"EC | ERC | HORIZON EUROPE European Research Council","grant_id":"957502","title":null},{"funder_name":"Fondazione AIRC per la ricerca sul cancro ETS","grant_id":"19891","title":null},{"funder_name":"Fondazione AIRC per la ricerca sul cancro ETS","grant_id":"22737","title":null},{"funder_name":"Ministero della Salute","grant_id":"RF‐2018‐12365801","title":null},{"funder_name":"Ministero dell'Università e della Ricerca","grant_id":"PE00000007,INF‐ACT","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"P01 AI060699","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI129269","title":null}],"total_grants":8,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.15252/emmm.202317580","host_type":"publisher"},{"url":"https://link.springer.com/content/pdf/10.15252/emmm.202317580.pdf","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.15252/emmm.202317580","host_type":"publisher"},{"url":"https://link.springer.com/article/10.15252/emmm.202317580/fulltext.html","host_type":"publisher"},{"url":"https://www.embopress.org/doi/pdf/10.15252/emmm.202317580","host_type":"publisher"},{"url":"https://air.unimi.it/bitstream/2434/963420/2/EMBO%20Mol%20Med%20-%202023%20-%20Fumagalli%20-%20Nirmatrelvir%20treatment%20of%20SARS%e2%80%90CoV%e2%80%902%e2%80%90infected%20mice%20blunts%20antiviral%20adaptive%20immune.pdf","host_type":"repository"},{"url":"https://iris.unica.it/bitstream/11584/360860/1/EMBO%20Mol%20Med%20-%202023%20-%20Fumagalli%20-%20Nirmatrelvir%20treatment%20of%20SARS%c3%a2%20%20CoV%c3%a2%20%202%c3%a2%20%20infected%20mice%20blunts%20antiviral%20adaptive%20immune-2.pdf","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10165354/pdf/EMMM-15-e17580.pdf","host_type":"repository"},{"url":"https://doaj.org/article/af6a4cf2e9764395b79666f9ed74a291","host_type":"repository"},{"url":"https://hdl.handle.net/11573/1706840","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC10165354","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC10165354?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":[],"mesh_terms":["B-Lymphocytes","Animals","Mice, Inbred C57BL","Mice","Lactams","Nitriles","Leucine","Proline","Antiviral Agents","Adaptive Immunity","COVID-19","SARS-CoV-2","Memory T Cells","COVID-19 Drug Treatment"],"keywords":["Antiviral treatment","Animal Models","adaptive immunity","Sars-cov-2","Nirmatrelvir"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T01:13:11.987829Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}