Rapid determination of the wide dynamic range of SARS-CoV-2 Spike T cell responses in whole blood of vaccinated and naturally infected

Tan, A. T.; Lim, J. M.; Le Bert, N.; Kunasegaran, K.; Chia, A.; Qui, M.; Tan, N.; Chia, W. N.; Alwis, R.; Ding, Y.; Ooi, E. E.; Wang, L.-F.; Chen, M. I.; Young, B.; Hsu, L. Y.; Low, J.; Lye, D.; Bertoletti, A.

doi:10.1101/2021.06.29.450293

bioRxiv · 10.1101/2021.06.29.450293

Rapid determination of the wide dynamic range of SARS-CoV-2 Spike T cell responses in whole blood of vaccinated and naturally infected

Tan, A. T.·Lim, J. M.·Le Bert, N.·Kunasegaran, K.·Chia, A.·Qui, M.·Tan, N.·Chia, W. N.·Alwis, R.·Ding, Y.·Ooi, E. E.·Wang, L.-F.·Chen, M. I.·Young, B.·Hsu, L. Y.·Low, J.·Lye, D.·Bertoletti, A.

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Abstract

BackgroundAntibodies and T cells cooperate to control virus infections. The definition of the correlates of protection necessary to manage the COVID-19 pandemic, require both immune parameters but the complexity of traditional tests limits virus-specific T cell measurements. MethodsWe test the sensitivity and performance of a simple and rapid SARS-CoV-2 Spike-specific T cell test based on stimulation of whole blood with peptides covering the SARS-CoV-2 Spike protein followed by cytokine (IFN-{gamma}, IL-2) measurement in different cohorts including BNT162b2 vaccinated (n=112; 201 samples), convalescent asymptomatic (n=62; 62 samples) and symptomatic (n=68; 115 samples) COVID-19 patients and SARS-CoV-1 convalescent individuals (n=12; 12 samples). ResultsThe sensitivity of the rapid cytokine whole blood test equates traditional methods of T cell analysis (ELISPOT, Activation Induced Markers). Utilizing this test we observed that Spike-specific T cells in vaccinated preferentially target the S2 region of Spike and that their mean magnitude is similar between them and SARS-CoV-2 convalescents at 3 months after vaccine or virus priming respectively. However, a wide heterogeneity of Spike-specific T cell magnitude characterizes the individual responses irrespective of the time of analysis. No correlation between neutralizing antibody levels and Spike-specific T cell magnitude were found. ConclusionsRapid measurement of cytokine production in whole blood after peptide activation revealed a wide dynamic range of Spike-specific T cell response after vaccination that cannot be predicted from neutralizing antibody quantities. Both Spike-specific humoral and cellular immunity should be tested after vaccination to define the correlates of protection necessary to evaluate current vaccine strategies.

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Tan, A. T., Lim, J. M., Le Bert, N., Kunasegaran, K., Chia, A., Qui, M., Tan, N., Chia, W. N., Alwis, R., Ding, Y., Ooi, E. E., Wang, L.-F., Chen, M. I., Young, B., Hsu, L. Y., Low, J., Lye, D., Bertoletti, A.. 2021-06-29. Rapid determination of the wide dynamic range of SARS-CoV-2 Spike T cell responses in whole blood of vaccinated and naturally infected. https://doi.org/10.1101/2021.06.29.450293

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