Introduction: Considering the reported efficacy of monoclonal antibodies (mAbs) directed against the Spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in reducing disease severity, the aim of this study was to investigate the innate immune response before and after mAbs treatment in 72 vaccinated and 31 unvaccinated SARS-CoV-2 patients. Methods: The mRNA levels of IFN-I, IFN-related genes and cytokines were evaluated using RT/real-time quantitative PCR. Results: Vaccinated patients showed increased rate of negative SARS-CoV-2 PCR tests on nasopharyngeal swab compared with unvaccinated ones after mAbs treatment (p = .002). Unvaccinated patients had lower IFN-α/ω and higher IFN-related genes (IFNAR1, IFNAR2, IRF9, ISG15, ISG56 and IFI27) and cytokines (IL-6, IL-10 and TGF-β) mRNA levels compared to vaccinated individuals before mAbs (p < .05 for all genes). Increased IFN-α/ω, IFNAR1, IFNAR2 and IRF9 levels were observed in unvaccinated patients after mAbs treatment, while the mRNA expression ISGs and IL-10 were reduced in all patients. Conclusion: These data suggest that anti-S vaccinated patients have increased levels of innate immune genes compared to unvaccinated ones. Also, gene expression changes in IFN genes after mAbs administration are different according to the vaccination status of patients.

Differential expression of type I interferon and inflammatory genes in SARS-CoV-2-infected patients treated with monoclonal antibodies / Maddaloni, Luca; Santinelli, Letizia; Bugani, Ginevra; G Cacciola, Elio; Lazzaro, Alessandro; M Lofaro, Chiara; Caiazzo, Sara; Frasca, Federica; Fracella, Matteo; Ajassa, Camilla; Leanza, Cristiana; Napoli, Anna; Cinti, Lilia; Gaeta, Aurelia; Antonelli, Guido; Ceccarelli, Giancarlo; Mastroianni, Claudio Maria; Scagnolari, Carolina; D'Ettorre, Gabriella. - In: IMMUNITY, INFLAMMATION AND DISEASE. - ISSN 2050-4527. - 11:10(2023), pp. 1-11. [10.1002/iid3.968]

Differential expression of type I interferon and inflammatory genes in SARS-CoV-2-infected patients treated with monoclonal antibodies

Luca Maddaloni
Writing – Original Draft Preparation
;
Letizia Santinelli;Ginevra Bugani;Alessandro Lazzaro;Federica Frasca;Matteo Fracella;Camilla Ajassa;Cristiana Leanza;Anna Napoli;Lilia Cinti;Aurelia Gaeta;Guido Antonelli;Giancarlo Ceccarelli
;
Claudio M Mastroianni;Carolina Scagnolari;Gabriella d'Ettorre
2023

Abstract

Introduction: Considering the reported efficacy of monoclonal antibodies (mAbs) directed against the Spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in reducing disease severity, the aim of this study was to investigate the innate immune response before and after mAbs treatment in 72 vaccinated and 31 unvaccinated SARS-CoV-2 patients. Methods: The mRNA levels of IFN-I, IFN-related genes and cytokines were evaluated using RT/real-time quantitative PCR. Results: Vaccinated patients showed increased rate of negative SARS-CoV-2 PCR tests on nasopharyngeal swab compared with unvaccinated ones after mAbs treatment (p = .002). Unvaccinated patients had lower IFN-α/ω and higher IFN-related genes (IFNAR1, IFNAR2, IRF9, ISG15, ISG56 and IFI27) and cytokines (IL-6, IL-10 and TGF-β) mRNA levels compared to vaccinated individuals before mAbs (p < .05 for all genes). Increased IFN-α/ω, IFNAR1, IFNAR2 and IRF9 levels were observed in unvaccinated patients after mAbs treatment, while the mRNA expression ISGs and IL-10 were reduced in all patients. Conclusion: These data suggest that anti-S vaccinated patients have increased levels of innate immune genes compared to unvaccinated ones. Also, gene expression changes in IFN genes after mAbs administration are different according to the vaccination status of patients.
2023
sars-cov-2; type I interferons; interferon-stimulated genes; monoclonal antibodies
01 Pubblicazione su rivista::01a Articolo in rivista
Differential expression of type I interferon and inflammatory genes in SARS-CoV-2-infected patients treated with monoclonal antibodies / Maddaloni, Luca; Santinelli, Letizia; Bugani, Ginevra; G Cacciola, Elio; Lazzaro, Alessandro; M Lofaro, Chiara; Caiazzo, Sara; Frasca, Federica; Fracella, Matteo; Ajassa, Camilla; Leanza, Cristiana; Napoli, Anna; Cinti, Lilia; Gaeta, Aurelia; Antonelli, Guido; Ceccarelli, Giancarlo; Mastroianni, Claudio Maria; Scagnolari, Carolina; D'Ettorre, Gabriella. - In: IMMUNITY, INFLAMMATION AND DISEASE. - ISSN 2050-4527. - 11:10(2023), pp. 1-11. [10.1002/iid3.968]
File allegati a questo prodotto
File Dimensione Formato  
Maddaloni_Differential-expression_2023.pdf

accesso aperto

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 2.18 MB
Formato Adobe PDF
2.18 MB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1692715
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 0
  • ???jsp.display-item.citation.isi??? 0
social impact