Cell Host & Microbe
Volume 30, Issue 3, 9 March 2022, Pages 388-399.e3
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Article
Development of a T cell-based immunodiagnostic system to effectively distinguish SARS-CoV-2 infection and COVID-19 vaccination status

https://doi.org/10.1016/j.chom.2022.02.003Get rights and content
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Highlights

  • A T cell-based assay allows discrimination of SARS-CoV-2 infection and vaccination

  • The classification scheme has high sensitivity and specificity and broad applicability

  • The use of SARS-CoV-2 epitope pools yield higher accuracy than serological readouts

  • Breakthrough infections can be effectively segregated from vaccine responses

Summary

Both SARS-CoV-2 infections and COVID-19 vaccines elicit memory T cell responses. Here, we report the development of 2 pools of experimentally defined SARS-CoV-2 T cell epitopes that, in combination with spike, were used to discriminate 4 groups of subjects with different SARS-CoV-2 infection and COVID-19 vaccine status. The overall T cell-based classification accuracy was 89.2% and 88.5% in the experimental and validation cohorts. This scheme was applicable to different mRNA vaccines and different lengths of time post infection/post vaccination and yielded increased accuracy when compared to serological readouts. T cell responses from breakthrough infections were also studied and effectively segregated from vaccine responses, with a combined performance of 86.6% across all 239 subjects from the 5 groups. We anticipate that a T cell-based immunodiagnostic scheme to classify subjects based on their vaccination and natural infection history will be an important tool for longitudinal monitoring of vaccinations and for establishing SARS-CoV-2 correlates of protection.

Keywords

SARS-CoV-2
T cells
epitope
viruses
COVID-19
vaccination
breakthrough infection
immunodiagnostic tool

Data and code availability

  • The datasets generated and analyzed in this study will be shared by the lead contact upon reasonable request. Additional supplemental items are available from Mendeley Data at https://doi.org/10.17632/s6gpnrmxg2.1.

  • This paper does not report original code.

  • Any additional information required to reanalyze the data reported in this work paper is available from the lead contact upon request.

Cited by (0)

5

These authors contributed equally

6

Lead contact