Distinguishing COVID-19 infection and vaccination history by T cell reactivity
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Abstract
SARS-CoV-2 infection and COVID-19 vaccines elicit memory T cell responses. Here, we report the development of two new pools of E xperimentally-defined T cell epitopes derived from the non-spike R emainder of the SARS-CoV-2 proteome (CD4RE and CD8RE). The combination of T cell responses to these new pools and Spike (S) were used to discriminate four groups of subjects with different SARS-CoV-2 infection and COVID-19 vaccine status: non-infected, non-vaccinated (I−V−); infected and non-vaccinated (I+V−); infected and then vaccinated (I+V+); and non-infected and vaccinated (I−V+). The overall classification accuracy based on 30 subjects/group was 89.2% in the original cohort and 88.5% in a validation cohort of 96 subjects. The T cell classification scheme was applicable to different mRNA vaccines, and different lengths of time post-infection/post-vaccination. T cell responses from breakthrough infections (infected vaccinees, V+I+) were also effectively segregated from the responses of vaccinated subjects using the same classification tool system. When all five groups where combined, for a total of 239 different subjects, the classification scheme performance was 86.6%. We anticipate that a T cell-based immunodiagnostic scheme able to classify subjects based on their vaccination and natural infection history will be an important tool for longitudinal monitoring of vaccination and aid in establishing SARS-CoV−2 correlates of protection.
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SciScore for 10.1101/2021.12.15.472874: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Human Subjects and PBMC isolation: The Institutional Review Boards of the University of California, San Diego (UCSD; 200236X) and the La Jolla Institute for Immunology (LJI; VD-214) approved the protocols used for blood collection for all the subjects who donated at all sites.
Consent: Each participant provided informed consent and was assigned a study identification number with clinical information recorded.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources AntI−human IgG peroxidase antibody produced in goat (Sigma A6029) was used at a 1:5,000 dilution. AntI−human IgG peroxidase …SciScore for 10.1101/2021.12.15.472874: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Human Subjects and PBMC isolation: The Institutional Review Boards of the University of California, San Diego (UCSD; 200236X) and the La Jolla Institute for Immunology (LJI; VD-214) approved the protocols used for blood collection for all the subjects who donated at all sites.
Consent: Each participant provided informed consent and was assigned a study identification number with clinical information recorded.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources AntI−human IgG peroxidase antibody produced in goat (Sigma A6029) was used at a 1:5,000 dilution. AntI−human IgG peroxidase antibodysuggested: NoneAntI−human IgGsuggested: NoneThe cells were stimulated with the different MPs analyzed (1ug/mL), PHA (10mg/mL), and DMSO (0.1%) in 96-well plates previously coated with antI−cytokine antibodies for IFNγ, (mAbs 1-D1K; Mabtech, Stockholm, Sweden) at a concentration of 10ug/mL. antI−cytokinesuggested: NoneSubsequently, plates were washed again with PBS/0.05% Tween20 and incubated for 1 hour with fluorophore-conjugated antibodies (AntI−BAM-490). AntI−BAM-490suggested: NoneSoftware and Algorithms Sentences Resources All samples were acquired on a ZE5 cell analyzer (Biorad laboratories, Hercules, CA) and analyzed with FlowJo software (Tree Star, Ashland, OR). FlowJosuggested: (FlowJo, RRID:SCR_008520)Statistical analysis: Experimental data were analyzed by GraphPad Prism Version 9 (La Jolla, CA) and Microsoft Excel Version 16.16.27 (Microsoft, Redmond, WA). GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Microsoft Excelsuggested: (Microsoft Excel, RRID:SCR_016137)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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