Exploratory analysis to identify the best antigen and the best immune biomarkers to study SARS-CoV-2 infection
Abstract Background Recent studies proposed the whole-blood based IFN-γ-release assay to study the antigen-specific SARS-CoV-2 response. Since the early prediction of disease progression could help to assess the optimal treatment strategies, an integrated knowledge of T-cell and antibody response la...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-06-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-021-02938-8 |
| _version_ | 1818848513199439872 |
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| author | Elisa Petruccioli Saeid Najafi Fard Assunta Navarra Linda Petrone Valentina Vanini Gilda Cuzzi Gina Gualano Luca Pierelli Antonio Bertoletti Emanuele Nicastri Fabrizio Palmieri Giuseppe Ippolito Delia Goletti |
| author_facet | Elisa Petruccioli Saeid Najafi Fard Assunta Navarra Linda Petrone Valentina Vanini Gilda Cuzzi Gina Gualano Luca Pierelli Antonio Bertoletti Emanuele Nicastri Fabrizio Palmieri Giuseppe Ippolito Delia Goletti |
| author_sort | Elisa Petruccioli |
| collection | DOAJ |
| description | Abstract Background Recent studies proposed the whole-blood based IFN-γ-release assay to study the antigen-specific SARS-CoV-2 response. Since the early prediction of disease progression could help to assess the optimal treatment strategies, an integrated knowledge of T-cell and antibody response lays the foundation to develop biomarkers monitoring the COVID-19. Whole-blood-platform tests based on the immune response detection to SARS-CoV2 peptides is a new approach to discriminate COVID-19-patients from uninfected-individuals and to evaluate the immunogenicity of vaccine candidates, monitoring the immune response in vaccine trial and supporting the serological diagnostics results. Here, we aimed to identify in the whole-blood-platform the best immunogenic viral antigen and the best immune biomarker to identify COVID-19-patients. Methods Whole-blood was overnight-stimulated with SARS-CoV-2 peptide pools of nucleoprotein-(NP) Membrane-, ORF3a- and Spike-protein. We evaluated: IL-1β, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL- 15, IL-17A, eotaxin, FGF, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF, RANTES, TNF-α, VEGF. By a sparse partial least squares discriminant analysis we identified the most important soluble factors discriminating COVID-19- from NO-COVID-19-individuals. Results We identified a COVID-19 signature based on six immune factors: IFN-γ, IP-10 and IL-2 induced by Spike; RANTES and IP-10 induced by NP and IL-2 induced by ORF3a. We demonstrated that the test based on IP-10 induced by Spike had the highest AUC (0.85, p < 0.0001) and that the clinical characteristics of the COVID-19-patients did not affect IP-10 production. Finally, we validated the use of IP-10 as biomarker for SARS-CoV2 infection in two additional COVID-19-patients cohorts. Conclusions We set-up a whole-blood assay identifying the best antigen to induce a T-cell response and the best biomarkers for SARS-CoV-2 infection evaluating patients with acute COVID-19 and recovered patients. We focused on IP-10, already described as a potential biomarker for other infectious disease such as tuberculosis and HCV. An additional application of this test is the evaluation of immune response in SARS-CoV-2 vaccine trials: the IP-10 detection may define the immunogenicity of a Spike-based vaccine, whereas the immune response to the virus may be evaluated detecting other soluble factors induced by other viral-antigens. |
| first_indexed | 2024-12-19T06:18:32Z |
| format | Article |
| id | doaj.art-e15b646c2b714ebda3b5315e7d625008 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-19T06:18:32Z |
| publishDate | 2021-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-e15b646c2b714ebda3b5315e7d6250082022-12-21T20:32:47ZengBMCJournal of Translational Medicine1479-58762021-06-0119111610.1186/s12967-021-02938-8Exploratory analysis to identify the best antigen and the best immune biomarkers to study SARS-CoV-2 infectionElisa Petruccioli0Saeid Najafi Fard1Assunta Navarra2Linda Petrone3Valentina Vanini4Gilda Cuzzi5Gina Gualano6Luca Pierelli7Antonio Bertoletti8Emanuele Nicastri9Fabrizio Palmieri10Giuseppe Ippolito11Delia Goletti12Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCSTranslational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCSClinical Epidemiology Unit, National Institute for Infectious Disease Lazzaro Spallanzani-IRCCSTranslational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCSTranslational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCSTranslational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCSClinical Division of Infectious Diseases, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCSUOC Transfusion Medicine and Stem Cell Unit, San Camillo Forlanini HospitalProgramme in Emerging Infectious Diseases, Duke-National University of Singapore Medical SchoolClinical Division of Infectious Diseases, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCSClinical Division of Infectious Diseases, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCSScientific Direction, National Institute for Infectious Disease “Lazzaro Spallanzani”-IRCCSTranslational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCSAbstract Background Recent studies proposed the whole-blood based IFN-γ-release assay to study the antigen-specific SARS-CoV-2 response. Since the early prediction of disease progression could help to assess the optimal treatment strategies, an integrated knowledge of T-cell and antibody response lays the foundation to develop biomarkers monitoring the COVID-19. Whole-blood-platform tests based on the immune response detection to SARS-CoV2 peptides is a new approach to discriminate COVID-19-patients from uninfected-individuals and to evaluate the immunogenicity of vaccine candidates, monitoring the immune response in vaccine trial and supporting the serological diagnostics results. Here, we aimed to identify in the whole-blood-platform the best immunogenic viral antigen and the best immune biomarker to identify COVID-19-patients. Methods Whole-blood was overnight-stimulated with SARS-CoV-2 peptide pools of nucleoprotein-(NP) Membrane-, ORF3a- and Spike-protein. We evaluated: IL-1β, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL- 15, IL-17A, eotaxin, FGF, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF, RANTES, TNF-α, VEGF. By a sparse partial least squares discriminant analysis we identified the most important soluble factors discriminating COVID-19- from NO-COVID-19-individuals. Results We identified a COVID-19 signature based on six immune factors: IFN-γ, IP-10 and IL-2 induced by Spike; RANTES and IP-10 induced by NP and IL-2 induced by ORF3a. We demonstrated that the test based on IP-10 induced by Spike had the highest AUC (0.85, p < 0.0001) and that the clinical characteristics of the COVID-19-patients did not affect IP-10 production. Finally, we validated the use of IP-10 as biomarker for SARS-CoV2 infection in two additional COVID-19-patients cohorts. Conclusions We set-up a whole-blood assay identifying the best antigen to induce a T-cell response and the best biomarkers for SARS-CoV-2 infection evaluating patients with acute COVID-19 and recovered patients. We focused on IP-10, already described as a potential biomarker for other infectious disease such as tuberculosis and HCV. An additional application of this test is the evaluation of immune response in SARS-CoV-2 vaccine trials: the IP-10 detection may define the immunogenicity of a Spike-based vaccine, whereas the immune response to the virus may be evaluated detecting other soluble factors induced by other viral-antigens.https://doi.org/10.1186/s12967-021-02938-8SARS-CoV-2COVID-19BiomarkersT-cellImmunityIP-10 |
| spellingShingle | Elisa Petruccioli Saeid Najafi Fard Assunta Navarra Linda Petrone Valentina Vanini Gilda Cuzzi Gina Gualano Luca Pierelli Antonio Bertoletti Emanuele Nicastri Fabrizio Palmieri Giuseppe Ippolito Delia Goletti Exploratory analysis to identify the best antigen and the best immune biomarkers to study SARS-CoV-2 infection Journal of Translational Medicine SARS-CoV-2 COVID-19 Biomarkers T-cell Immunity IP-10 |
| title | Exploratory analysis to identify the best antigen and the best immune biomarkers to study SARS-CoV-2 infection |
| title_full | Exploratory analysis to identify the best antigen and the best immune biomarkers to study SARS-CoV-2 infection |
| title_fullStr | Exploratory analysis to identify the best antigen and the best immune biomarkers to study SARS-CoV-2 infection |
| title_full_unstemmed | Exploratory analysis to identify the best antigen and the best immune biomarkers to study SARS-CoV-2 infection |
| title_short | Exploratory analysis to identify the best antigen and the best immune biomarkers to study SARS-CoV-2 infection |
| title_sort | exploratory analysis to identify the best antigen and the best immune biomarkers to study sars cov 2 infection |
| topic | SARS-CoV-2 COVID-19 Biomarkers T-cell Immunity IP-10 |
| url | https://doi.org/10.1186/s12967-021-02938-8 |
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