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

Abstract

Background: Antibodies 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. Methods: We 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-γ, 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). Results: The 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. Conclusions: Rapid 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.

Degenerate CD8 Epitopes Mapping to Structurally Constrained Regions of the Spike Protein: A T Cell-Based Way-Out From the SARS-CoV-2 Variants Storm

“…Although the CD8 epitopes discussed in this section have originally been identified in infected and convalescent patients, available studies in vaccinees (43,(80)(81)(82)(83) confirm a substantial enrichment of CD8 T cell epitopes within the S2 domain, which contrasts with the lower CD8 epitope representation found in the S1 N-terminal domain (83).…”

Finger stick blood test to assess postvaccination SARS‐CoV‐2 neutralizing antibody response against variants

“…Therefore, both humoral and cellular immune response are required for a complete assessment of SARS-CoV-2 immunity. While standardized methods for rapid assessment of cellular immunity responses are underway,26 nAb level measurement remains a reliable indicator for immune protection at PoC level and deems to be critical at this point. It has been estimated that 90% of convalescent plasma/sera's neutralizing activity targets the immunodominant RBD,[27][28][29] hence the current modified cpVNT format that measures the nAb response to RBD-associated mutations represents a good proxy for assessing individual's immune protection.…”